Imaging brain plasticity after trauma

The brain is highly plastic after stroke or epilepsy; however, there is a paucity of brain plasticity investigation after traumatic brain injury （TBI）. This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrat- ed both structural reorganization as well as functional compensation by the recruitment of other brain regions. However, the large scale brain network alterations after TBI are still unknown, and the field is still short of proper means on how to guide the choice of TBI rehabilitation or treat- ment plan to promote brain plasticity. The authors also point out the new direction of brain plas- ticity investigation.

Fractionated resection on low grade gliomas involving Broca＇s area and insights to brain plasticity

Background Resent advances on functional mapping have enabled us to conduct surgery on gliomas within the eloquent area. The objective of the article is to discuss the feasibility of a planned fractionated strategy of resection on low-grade gliomas （LGGs） involving Broca＇s area. We report the first surgical series of planned fractionated resections on LGGs within Broca＇s area, focusing on language functional reshaping. Methods Four patients were treated with fractionated operations for LGGs involving Broca＇s area. All cases underwent conventional magnetic resonance （MR） scanning, language functional MR and diffusion tensor imaging （DTI） before operation. The resections were then performed on patients under awake anesthesia using intraoperative electrical stimulation （IES） for functional mapping. Pre- and post-operative neuro-psychological examinations were evaluated.Results Total resections were achieved in all cases as confirmed by the postoperative control MR. After transient language worsening, all patients recovered to normal 3-6 months later. Language functional MR scannings have shown language functional cortical and subcortical pathway reorganization （in the perilesion or contra-lateral hemisphere） after the operation. All patients returned to a normal socioprofessional life. Conclusions By utilizing the dynamic interaction between brain plasticity and fractionated resections, we can totally remove the tumor involving Broca＇s structure without inducing permanent postoperative deficits and even improve the quality of life.

Cell cycle reactivation in mature neurons: a link with brain plasticity, neuronal injury and neurodegenerative diseases?

Although the cell cycle machinery is essentially linked to cellular proliferation, recent findings suggest that neuronal cell death is frequently concurrent with the aberrant expression of cell cycle proteins in post-mitotic neurons. The present work reviews the evidence of cell cycle reentry and expression of cell cycle-associated proteins as a complex response of neurons to insults in the adult brain but also as a mechanism underlying brain plasticity. The basic aspects of cell cycle mechanisms, as well as the evidence showing cell cycle protein expression in the injured brain, are reviewed. The discussion includes recent experimental work attempting to establish a correlation between altered brain plasticity and neuronal death, and an analysis of recent evidence on how neural cell cycle dysregulation is related to neurodegenerative diseases especially the Alzheimer＇s disease. Understanding the mechanisms that control reexpression of proteins required for cell cycle progression which is involved in brain remodeling, may shed new light into the mechanisms involved in neuronal demise under diverse pathological circumstances. This would provide valuable clues about the possible therapeu tic targets, leading to potential treatment of presently challenging neurodegenerative diseases.

Basic Research on Brain Development and Neural Plasticity Kicked Off

A major basic research projectin the field of neurosciencewas launched on November26 last year at the Shanghai-basedInstitute of Neuroscience of the Chi-nese Academy of Sciences(CAS).

Structural remodeling in related brain regions in patients with facial synkinesis

Facial synkinesis is a troublesome sequelae of facial nerve malfunction.It is difficult to recover from synkinesis,despite improved surgical techniques for isolating the peripheral facial nerve branches.Furthermore,it remains unclear whether long-term dysfunction of motor control can lead to irreversible plasticity-induced structural brain changes.This case-control study thus investigated the structural brain alterations associated with facial synkinesis.The study was conducted at Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China.Twenty patients with facial synkinesis(2 male and 18 female,aged 33.35±6.97 years)and 19 healthy volunteers(2 male and 17 female,aged 33.21±6.75 years)underwent magnetic resonance imaging,and voxel-based and surface-based morphometry techniques were used to analyze data.There was no significant difference in brain volume between patients with facial synkinesis and healthy volunteers.Patients with facial synkinesis exhibited a significantly reduced cortical thickness in the contralateral superior and inferior temporal gyri and a reduced sulcal depth of the ipsilateral precuneus compared with healthy volunteers.In addition,sulcal depth of the ipsilateral precuneus was negatively correlated with the severity of depression.These findings suggest that there is a structural remodeling of gray matter in patients with facial synkinesis after facial nerve malfunction.This study was approved by the Ethics Review Committee of the Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China(approval No.2017-365-T267)on September 13,2017,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR1800014630)on January 25,2018.

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

One of the most important causes of brain injury in the neonatal period is a perinatal hypoxicischemic event.This devastating condition can lead to long-term neurological deficits or even death.After hypoxic-ischemic brain injury,a variety of specific cellular mechanisms are set in motion,triggering cell damage and finally producing cell death.Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury.After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury,various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.Among them,the endocannabinoid system emerges as a natural system of neuroprotection.The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury,acting as a natural neuroprotectant.The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury,and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury,substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

Contralateral S1 function is involved in electroacupuncture treatment-mediated recovery after focal unilateral M1 infarction

Acupuncture at acupoints Baihui(GV20)and Dazhui(GV14)has been shown to promote functional recovery after stroke.However,the contribution of the contralateral primary sensory cortex(S1)to recovery remains unclear.In this study,unilateral local ischemic infarction of the primary motor cortex(M1)was induced by photothrombosis in a mouse model.Electroacupuncture(EA)was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques.Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction.Intrinsic neuronal excitability and activity were also disturbed,which was rescued by EA.Furthermore,the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1.We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction.Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction.The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine(approval No.20200407009)April 7,2020.

Perilesional reorganization of motor function in stroke patients

Perilesional reorganization is an important recovery mechanism for stroke patients because it yields good motor outcomes. However, perilesional reorganization remains poorly understood. The scientific basis for stroke rehabilitation can be established when detailed mechanisms of recovery are clarified. In addition, studies at the subcortical level remain in the early stages. Therefore, the present study suggested that additional investigations should focus on perilesional reorganization at the subcortical level, identifying the critical period for this mechanism and determining treatment strategies and modalities to facilitate development. The present study reviews literature focused on perilesional reorganization in stroke patients with regard to demonstration, clinical characteristics, and rehabilitative aspects, as well as previous studies of perilesional reorganization at cortical and subcortical levels.

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury（SCI）. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI（mean age 40.94 ± 14.10 years old; male：female, 7：11） and 18 healthy subjects（37.33 ± 11.79 years old; male：female, 7：11） were studied by resting state functional magnetic resonance imaging. Gray matter volume（GMV） and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex（BA1） and left primary motor cortex（BA4）, and left BA1 and left somatosensory association cortex（BA5） was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-ROC-17013566）.

Proteomic analysis of trans-hemispheric motor cortex reorganization following contralateral C7 nerve transfer

Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Pre- vious studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth asso- ciated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer. Isobaric tags for relative and absolute quantitation and western blot assay were then used to screen differentially expressed proteins in bilateral motor cortices. We found that most differentially expressed proteins in both cortices of upper limb were associated with nervous system development and function （including neuron differentiation and development, axonogenesis, and guidance）, microtubule and cytoskeleton organization, synapse plasticity, and transmission of nerve impulses. Two key differentially expressed proteins, neurofilament light （NFL） and Thy-1, were identified. In contralateral cortex, the NFL level was upregulated 2 weeks after transfer and downregulated at 1 and 5 months. The Thy-1 level was upregulated from 1 to 5 months. In the affected cortex, the NFL level increased gradually from 1 to 5 months. Western blot results of key differentially expressed proteins were consistent with the proteom- ic findings. These results indicate that NFL and Thy-1 play an important role in trans-hemispheric organization following total brachial plexus root avulsion and contralateral C7 nerve transfer.

Perilesional reorganization of somatosensory function following traumatic cortical contusion A case report

The present study reports on a 23-year-old male patient with somatosensory dysfunction of the left hand following cortical contusion. His somatosensory dysfunction recovered to a nearly normal state at 6 months after injury. Functional MRI results demonstrated that the contralateral primary sensorimotor cortex centered on the primary somatosensroy cortex was activated during touch stimulation of the patient＇s right hand and either hand of control subjects. By contrast, the anterior area of the lesion centered on the precentral knob in the right hemisphere was activated during touch stimulation of the left hand. These findings show that the somatosensory function of the affected hand appears to have been recovered by the somatosensory cortex reorganizing into the anterior area of the contused primary somatosensory cortex.

Loss of micro RNA-124 expression in neurons in the peri-lesion area in mice with spinal cord injury

Micro RNA-124（mi R-124） is abundantly expressed in neurons in the mammalian central nervous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and postnatal neural differentiation. However, the expression profile of mi R-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of mi R-124 in mouse brain and spinal cord after spinal cord injury using in situ hybridization. Furthermore, the expression of mi R-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The mi R-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with Neu N immunohistochemical staining. The mi R-124 was mainly expressed in neurons throughout the brain and spinal cord. The expression of mi R-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were Neu N＋/mi R-124-. Moreover, the neurons distal to the peri-lesion site were Neu N＋/mi R-124＋. These findings indicate that mi R-124 expression in neurons is reduced after spinal cord injury, and may reflect the severity of spinal cord injury.

Recovery mechanisms of somatosensory function in stroke patients: implications of brain imaging studies

Somatosensory dysfunction is associated with a high incidence of functional impairment and safety in patients with stroke. With developments in brain mapping techniques, many studies have addressed the recovery of various functions in such patients. However, relatively little is known about the mechanisms of recovery of somatosensory function. Based on the previous human studies, a review of 11 relevant studies on the mecha- nisms underlying the recovery of somatosensory function in stroke patients was conducted based on the fol- lowing topics： （1） recovery of an injured somatosensory pathway, （2） peri-lesional reorganization, （3） contribu- tion of the unaffected somatosensory cortex, （4） contribution of the secondary somatosensory cortex, and （5） mechanisms of recovery in patients with thalamic lesions. We believe that further studies in this field using combinations of diffusion tensor imaging, functional neuroimaging, and magnetoencephalography are needed. In addition, the clinical significance, critical period, and facilitatory strategies for each recovery mechanism should be clarified.

Phenotypic plasticity Gasterosteus aculeatus ence in captivity of the threespine stickleback telencephalon in response to experi-

Threespine stickleback were used to examine phenotypic plasticity of telencephala in relation to inferred ecology. Fish from derived, allopatric, freshwater populations were sampled from three shallow, structurally complex lakes with ben- thic-foraging stickleback （benthics） and from three deep, structurally simple lakes with planktivores （limnetics）. The telencepha- Ion of specimens preserved immediately after capture （field-preserved）, field-caught fish held in aquaria for 90 days （lab-held）, and lab-bred fish from crosses and raised in aquaria were compared. Field-preserved sea-run （ancestral） stickleback were col- lected from two separate sites, and parents of lab-bred sea-run stickleback were collected from one of these sites. In field-preserved and lab-held fish, the telencephala of limnetics exhibited triangular dorsal shape, while those of benthics and sea-run fish had rounder shapes. No such pattern was detected in lab-bred fish. Within each treatment type, benthics had larger relative telencephalon sizes, using overall brain size as the covariate, than limnetics. Among field-preserved samples, sea-run fish had smaller telencephalon sizes than lake fish. Intra-population analyses of lake samples showed that field-preserved fish consis- tently had larger relative telencephalon sizes than lab-bred fish. The opposite was true of the sea-run population. In a separate study using one benthic population and one limnetic population, samples were preserved in the field immediately or held in the lab for 30, 60, and 90 days before they were sacrificed. In both populations, the telencephalon shapes of lab-held fish were similar to those of field-preserved fish but became progressively more like lab-bred ones over 90 days. In contrast, relative telencephalon size decreased dramatically by 30 days after which there was littie change. In freshwater threespine stickleback, the telencephalon exhibits considerable phenotypic plasticity, which was probably present in the ancestor [Current Zoology 58 （1）： 189-210, 2012].

针刺通过调节脑可塑性相关信号缓解脑卒中肢体痉挛状态研究进展

Stroke may cause upper motor neurons lesions, and thus limb spasm may occur. Brain plasticity refers to the brain's ability to change and adapt the environment and experience when the nervous system is damaged. Acupuncture can relieve the relevant pathological status due to stroke by enhancing brain plasticity. Specifically, acupuncture may finally achieve the balance between excitatory and inhibitory neurotransmitters by inhibiting the expression of neurotransmitter GABA, neurotrophic factor BDNF and proteins related to synaptic plasticity. This article analyzed and summarized that taking advantage of nervous plasticity the acupuncture could regenerate nervous cells and restore the related regulation of the movement by upper motor neurons, so as to relieving limb spasticity. It also summarized the research and application of acupuncture in regulating related signals, providing a systematic thought for the future study on acupuncture in the treatment of stroke induced limb.

Study on the Correlation between Synaptic Reconstruction and Astrocyte after Ischemia and the Influence of Electroacupuncture on Rats

Objective： To observe the effects of electroacupuncture （EA） on the structure parameters of synapse and reactive changes of astrocyte in the marginal zone of focal cerebral ischemia in rats at different time zones so as to further explore its underlying mechanisms in the treatment of cerebral ischemia. Methods： Ninety male Wistar rats were randomly assigned to sham-operation, model, and EA groups, with 30 animals in each group. Each group was subdivided into 1 h, as well as 1, 3, 7, and 21 days post-operation groups, with 6 animals assigned to each time point subgroup. Heat coagulation-induced occlusion of the middle cerebral artery was performed to establish a model of focal cerebral ischemia. EA was applied immediately following surgery to the EA group [4/20 Hz, 2.0-3.0 V, 1-3 mA, to Baihui （GV20） and Dazhui （GV14）] for 30 min. Treatment was performed once a day, and experimental animals were sacrificed at 1 h, as well as 1, 3, 7 and 21 days postoperation. The ultrastructure changes in synapse and astrocytes were observed by using transmission electron microscopy. Glial fibrillary acidic protein （GFAP） expression and Ca2＋ of astrocytes were measured by using laser confocal scanning microscope. Excitatory amino acid transporters-2 （EAAT2） and connexin 43 （CX43） expressions were assayed with immunohistochemical method. Canonical correlation analysis was conducted between structure parameters of synapse and parameters of astrocyte in the same time and group. Results： Broken synapses were observed following cerebral ischemia, and the numbers of synapses were significantly decreased. Compared with the model group, synaptic ultrastructure was significantly improved in the EA group. Compared with the sham-operation group, synaptic number density was significantly decreased, as were postsynaptic density thickness, synaptic cleft width and synaptic interface curvature in the EA and model groups. However, compared with the model group, postsynaptic density thickness was significantly increased in the EA group at the same time points post-operation （P〈0.05, P〈0.01）. In addition, synaptic cleft width, synaptic number density and synaptic interface curvature were significantly increased with the passage of time （P〈0.05, P〈0.01）. The expression of GFAP in the EA group were significantly lower than those in the model group at all the time points （P〈0.05, P〈0.01）. OD values of EAAT2 in the EA group were significantly higher than those in the model group at the same time （P〈0.05, P〈0.01）. Compared with that in the model group, the expressions of CX43 in the EA group increased significantly at 3 days and 7 days （P〈0.05, P〈0.01）. Ca2＋ average fluorescence intensity of astrocytes in the EA group was significantly lower than those in the model group at 1 h, 1 day, 3 days and 7 days （P〈0.05, P〈0.01）. The changes in structure parameters of synapse were closely related to the changesof CX43, EAAT2, GFAP, Ca＋ of astrocytes by EA treatment at all the time points. Conclusions： EA is helpful for synaptic reorganization, which may be related to its effect on intervening the activation state of astrocytes and promoting the beneficial interaction between astrocytes and synapses. Acupuncture could start the adjustment of neuron-glial network so as to promote the synaptic reorganization, which may be the key mechanism of treating cerebral ischemia.

Increased representation of the non-dominant hand in pianists demonstrated by measurement of 3D morphology of the central sulcus

Background:Post-mortem and magnetic resonance imaging(MRI)studies of the central sulcus,as an indicator of motor cortex,have shown that in the general population there is greater representation of the dominant compared to the non-dominant hand.Studies of musicians,who are highly skilled in performing complex finger movements,have suggested this dominance is affected by musical training,but methods and findings have been mixed.Objective:In the present study,an automated image analysis pipeline using a 3D mesh approach was applied to measure central sulcus(CS)asymmetry on MR images obtained for a cohort of right-handed pianists and matched controls.Methods:The depth,length,and surface area(SA)of the CS and thickness of the cortical mantle adjacent to the CS were measured in each cerebral hemisphere by applying the BrainVISA Morphologist 2012 software pipeline to 3D T1-weighted MR images of the brain obtained for 15 right-handed pianists and 14 controls,matched with respect to age,sex,and handedness.Asymmetry indices(AIs)were calculated for each parameter and multivariate analysis of covariance(MANCOVA),and post hoc tests were performed to compare differences between the pianist and control groups.Results:A one-way MANCOVA across the four AIs,controlling for age and sex,revealed a significant main effect of group(P=0.04),and post hoc analysis revealed that while SA was significantly greater in the left than the right cerebral hemisphere in controls(P<0.001),there was no significant difference between left and right SA in the pianists(P=0.634).Independent samples t-tests revealed that the SA of right CS was significantly larger in pianists compared to controls(P=0.015),with no between-group differences in left CS.Conclusions:Application of an image analysis pipeline to 3D MR images has provided robust evidence of sig-nificantly increased representation of the non-dominant hand in the brain of pianists compared to age-,sex-,and handedness-matched controls.This finding supports prior research showing structural differences in the central sulcus in musicians and is interpreted to reflect the long-term motor training and high skill level of right-handed pianists in using their left hand.