Reperfusion after hypoxia-ischemia exacerbates brain injury with compensatory activation of the antiferroptosis system:based on a novel rat model

Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats.First,based on the conventional RiceVannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge.Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins.We also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial cristae.Further,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage.Finally,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury.Based on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion.Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.

Hypoxia-ischemia in the immature rodent brain impairs serotonergic neuronal function in certain dorsal raphé nuclei

Neonatal hypoxia-ischemia(HI)results in losses of serotonergic neurons in specific dorsal raphe nuclei.However,not all serotonergic raphe neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate.The main objective of this study was to determine how serotonergic neurons,remaining in the dorsal raphe nuclei after neonatal HI,respond to an external stimulus(restraint stress).On postnatal day 3(P3),male rat pups were randomly allocated to one of the following groups:(i)control+no restraint(n=5),(ii)control+restraint(n=6),(iii)P3 HI+no restraint(n=5)or(iv)P3 HI+restraint(n=7).In the two HI groups,rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6%O2 for 30 minutes.Six weeks after P3 HI,on P45,rats were subjected to restraint stress for 30 minutes.Using dual immunolabeling for Fos protein,a marker for neuronal activity,and serotonin(5-hydroxytrypamine;5-HT),numbers of Fos-positive 5-HT neurons were determined in five dorsal raphe nuclei.We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphe nuclei compared to control animals.However,following P3 HI,the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphe ventrolateral,interfascicular and ventral nuclei compared with control animals exposed to restraint stress.In contrast,numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphe dorsal and caudal nuclei were not affected by P3 HI.These data indicate that not only are dorsal raphe serotonergic neurons lost after neonatal HI,but also remaining dorsal raphe serotonergic neurons have reduced differential functional viability in response to an external stimulus.Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC)on February 27,2009.

Influence of hypoxia-inducible factor 1-alpha on neuronal apoptosis in a rat model of hypoxia-or hypoxia-ischemia-induced brain injury

BACKGROUND: In addition to neuroprotective genes, the targeted genes of hypoxia-induciblefactor 1α (HIF-1α) include pro-apoptotic genes. However, the influence of HIF-1α on neuronalapoptosis in hypoxia-ischemia remains poorly understood.OBJECTIVE: To investigate the relationship between HIF-1α expression and neuronal apoptosis inhypoxia or hypoxia-ischemia brain injury and to determine the role of HIF-1α in regulating neuronalapoptosis.DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at theLaboratory of Children Neurology of Sichuan University between May 2006 and May 2007.MATERIALS: In situ cell death detected kit was provided by Roche, USA; rabbit anti-mouse HIF-1αpolyclonal antibody was purchased from Santa Cruz Biotechnologies, USA; rabbit anti-mousecleaved caspase-3 polyclonal antibody was purchased from Chemicon, USA.METHODS: A total of 36 Sprague Dawley rats aged 10 days were randomly assigned to 3 groups:sham-surgery, hypoxia, and hypoxia-ischemia, with 12 rats per group. The rats were treated at 3time points: 4, 8, and 24 hours, with 4 rats per time point. In the hypoxia-ischemia group, the rightcommon carotid artery was exposed and permanently ligated through a midline cervical incision. A2.5-hour exposure to hypoxia (8% O_2/92% N_2) was used to induce hypoxia-ischemia injury. In thehypoxia group, rats were exposed to hypoxia without ligation of the common carotid artery. In thesham-surgery group, the common carotid artery was exposed without ligation or hypoxia.MAIN OUTCOME MEASURES: Histopathological changes, HIF-1α and activated caspase-3 proteinexpression, integrated optical density of positive cells, and apoptosis-positive cells.RESULTS: Hematoxylin and eosin staining showed that neuronal degeneration and edema wasmost prominent at 24 hours after hypoxia-ischemia. HIF-1α protein expression was significantlyupregulated at 4 hours, peaked at 8 hours, and decreased at 24 hours after hypoxia orhypoxia-ischemia. HIF-1α protein expression was significant greater in the hypoxia andhypoxia-ischemia groups compared with the sham-surgery group (P < 0.01). Activated caspase-3protein expression began to increase at 4 and 8 hours following hypoxia or hypoxia-ischemia andwas significantly upregulated at 24 hours. Activated caspase-3 protein expression remained at lowlevels in the sham controls compared with the hypoxia and hypoxia-ischemia groups (P< 0.01).TUNEL staining showed that the number of apoptotic cells significantly increased at 24 hours afterhypoxia or hypoxia-ischemia. In addition, HIF-1α protein expression was greater in the hypoxiagroup compared with the hypoxia-ischemia group at the same time point (P< 0.05). However,activated caspase-3 expression and the number of TUNEL-positive cells were less in the hypoxiagroup compared with the hypoxia-ischemia group at the same time point (P < 0.05).CONCLUSION: HIF-1α played a neuroprotective role following hypoxia-ischemia brain injury.

Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits after hypoxia-ischemia-induced brain damage in newborn rats

Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage(HIBD).However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the left common carotid artery was ligated in neonatal rats,and the rats were subjected to hypoxia for 2 hours.Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine(10 m M in 10 μL) or the autophagy stimulator rapamycin(1 g/kg) 1 hour before artery ligation.Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR 1,but by reduced expression of GluR 2.Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury,whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury.Additionally,3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of Glu R1 and downregulation of GluR2 in the hippocampus.By contrast,rapamycin further elevated hippocampal Glu R1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD.Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats,at least in part,through normalizing Glu R1 and GluR2 expression.

Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

BACKGROUND:Exogenous ganglioside-1(GM1) can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage.OBJECTIVE:To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass,pathological morphology,growth-associated protein-43 expression,and neurobehavioral manifestations.DESIGN,TIME AND SETTING:A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute,Children's Hospital of Chongqing Medical University from August 2005 to August 2006.MATERIALS:A total of 36 neonatal,7-day-old,Sprague Dawley rats were used in this experiment.The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery,followed by oxygen inhalation at a low concentration(8% O2,92% N2) for 2 hours.METHODS:All rats were randomly divided into the following groups:GM1,model,and sham operation,with 12 rats each group.Rats in the GM1 and model groups received hypoxic/ischemic-induced brain damage.Rats in the GM1 group received injections of GM1(i.p.,20 mg/kg) at 0,24,48,72,96,120,and 144 hours following models established,and rats in the model group were administered(i.p.) the same amount of saline.The right carotid artery was separated,but not ligated,in the sham operation group rats.MAIN OUTCOME MEASURES:At 1 week after surgery,expression of growth-associated protein-43,a marker of neural development and plasticity,was detected in the hippocampal CA3 region by immunohistochemistry.Brain mass was measured,and the pathological morphology was observed.At 4 weeks after surgery,behavioral changes in the remaining rats were tested by Morris water maze,and growth-associated protein-43 expression was measured.RESULTS:(1) In the GM1 and sham operation groups,growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery(P < 0.05).In all three groups,brain weight of the right hemisphere was significantly less than the left hemisphere,in particular in the model group(P < 0.05).In the GM1 group,the weight difference between two hemispheres,as well as the extent of damage in the right hemisphere,was less than the model group(P < 0.01).In the sham operation group,brain tissue consisted of integrated structures and ordered cells.In the model group,the cerebral cortex layers of the right hemisphere were not defined,neurons were damaged,and neurons were disarranged in the hippocampal area.In the GM1 group,neurons were dense in the right cerebral cortex and hippocampal area,with no significant change in glial proliferation.(2) The average time of escape latency in the GM1 group was shortened 4 weeks after surgery,and significantly less than the model group(P < 0.05).In addition,the frequency platform passing in the GM1 group was significantly greater than the model group(P < 0.01).CONCLUSION:Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats.This protection may be associated with increased growth-associated protein-43 expression,which is involved in neuronal remodeling processes.

Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.

Epileptic brain network mechanisms and neuroimaging techniques for the brain network

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal discharges.Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice.An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic networks.In this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

Advantages of nanocarriers for basic research in the field of traumatic brain injury

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

The role of snapin in regulation of brain homeostasis

Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Application of artificial hibernation technology in acute brain injury

Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.

Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.

Effect of cognitive training on brain dynamics

The human brain is highly plastic.Cognitive training is usually used to modify functional connectivity of brain networks.Moreover,the structures of brain networks may determine its dynamic behavior which is related to human cognitive abilities.To study the effect of functional connectivity on the brain dynamics,the dynamic model based on functional connections of the brain and the Hindmarsh–Rose model is utilized in this work.The resting-state fMRI data from the experimental group undergoing abacus-based mental calculation(AMC)training and from the control group are used to construct the functional brain networks.The dynamic behavior of brain at the resting and task states for the AMC group and the control group are simulated with the above-mentioned dynamic model.In the resting state,there are the differences of brain activation between the AMC group and the control group,and more brain regions are inspired in the AMC group.A stimulus with sinusoidal signals to brain networks is introduced to simulate the brain dynamics in the task states.The dynamic characteristics are extracted by the excitation rates,the response intensities and the state distributions.The change in the functional connectivity of brain networks with the AMC training would in turn improve the brain response to external stimulus,and make the brain more efficient in processing tasks.

Management of Traumatic Brain Injuries at the Kara Regional Hospital

Introduction: Traumatic Brain Injury (TBI) is a major public health problem causing significant morbidity and mortality in young adults. This study aimed to describe the epidemiological, diagnostic, therapeutic, and evolutionary aspects of TBI. Materials and Methods: This was a prospective, descriptive study conducted from 1 April 2022 to 31 March 2023 on patients admitted to and treated for cranioencephalic trauma in the General Surgery department of Kara Regional Hospital. Results: Eighty-three (83) patients with cranioencephalic trauma were managed out of 773 patients admitted to the department during the study period. The mean age was 34 ± 14.98 years and the sex ratio was 3.6 in favour of men. Motorbike taxi drivers were the social group most affected (n = 33, 40%). The causes of trauma were dominated by public road accidents (n = 80;96%). TBI was mild (n = 40;48%), moderate (n = 35;42%) and severe (n = 8;10%). Cerebral CT scans were performed in 19 patients (23%). Cerebral contusion (n = 4) was the most frequent cerebral lesion. Six patients (7%) with severe head injuries were transferred to Kara University Hospital. Six deaths (7%) occurred in patients with severe head injuries. The main sequelae were intermittent headaches in all patients reviewed, and memory problems (6%). Conclusion: Traumatic brain injuries are common at Kara Regional Hospital. Severe cranial trauma is less frequent but leads to death because of financial difficulties and limited technical facilities.

Neurotrophins and neural stem cells in posttraumatic brain injury repair

Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics.

Neuropsychological Profile of a Patient with Acquired Brain Damage Following Vascular Lesion of the Left Anterior Cingulate Cortex

Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of action.Material&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro.Our primary objective is to provide evidence supporting the clinical application of PDMSCs.Results:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after CCI.PDMSCs,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal vein.This intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted rats.In the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media.Notably,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2.Conclusion:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

Expectations and Level of Satisfaction of the Patient with Parkinson’s Disease Undergoing Deep Brain Stimulation Surgery at the National Institute of Neurology and Neurosurgery

Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.