Role of disturbance coefficient in monitoring and treatment of cerebral edema in patients with cerebral hemorrhage

BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.

Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Revisiting cerebral endothelial cells in Alzheimer’s disease

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.

Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic surgery.Although cerebral fat embolism(CFE)as a complication is rare,it carries serious health risks.CASE SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling surgery.After the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided weakness.Comprehensive physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon admission.The clinical diagnosis was acute cerebral embolism following facial fat filling surgery.Treatment included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb function.The patient showed a significant improvement in symptoms after 2 weeks of treatment.She recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of headache.CONCLUSION Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial reconstruction.To prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

Role of nitric oxide in cerebral ischemia/reperfusion injury:A biomolecular overview

Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.

Role of triggering receptor expressed on myeloid cells 1/2 in secondary injury after cerebral hemorrhage

Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Inhibition of the cGAS–STING pathway:contributing to the treatment of cerebral ischemia-reperfusion injury

The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.

Cerebral complications after unilateral biportal endoscopic surgery:A case report

BACKGROUND Unilateral biportal endoscopic(UBE)surgery has developed rapidly during the past decade.Continuous epidural space irrigation is generally considered the principal reason for cerebral complications following UBE surgery.We present a case of mental symptoms during the general anesthesia awakening period due to pneumocephalus.CASE SUMMARY A 70-year-old woman with lumbar disc herniation underwent UBE surgery stably under general anesthesia.Uncontrollable hypertension occurred immediately after transfer to the postoperative care unit,accompanied by increased heart rate and tachypnea.During the recovery process,the patient responded to external stimuli but was confused and unable to complete command actions.Neck stiff-ness and significantly increased muscle strength on the left side indicated the presence of de-cerebrate rigidity.An urgent brain computed tomography scan showed pneumocephalus compressing the brainstem.After receiving analgesia and sedation treatment,the patient was conscious three hours later and recovered rapidly.She was discharged on the fifth postoperative day and followed up for 3 months with no surgical or brain complications.CONCLUSION Cerebral complications emerging during the general anesthesia awakening period following UBE surgery are not entirely due to increased intracranial pressure.Pneumocephalus induced by dural injury may also be a potential cause.

Comparison of the effect of ranibizumab in retinal vein occlusion and macular edema with different optical coherence tomographic patterns

AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.

SMAD specific E3 ubiquitin protein ligase 1 accelerates diabetic macular edema progression by WNT inhibitory factor 1

BACKGROUND Diabetic macular edema(DME)is the most common cause of vision loss in people with diabetes.Tight junction disruption of the retinal pigment epithelium(RPE)cells has been reported to induce DME development.SMAD-specific E3 ubiquitin protein ligase(SMURF)1 was associated with the tight junctions of cells.However,the mechanism of SMURF1 in the DME process remains unclear.AIM To investigate the role of SMURF1 in RPE cell tight junction during DME.METHODS ARPE-19 cells treated with high glucose(HG)and desferrioxamine mesylate(DFX)for establishment of the DME cell model.DME mice models were constructed by streptozotocin induction.The trans-epithelial electrical resistance and permeability of RPE cells were analyzed.The expressions of tight junction-related and autophagy-related proteins were determined.The interaction between insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)and SMURF1 mRNA was verified by RNA immunoprecipitation(RIP).SMURF1 N6-methyladenosine(m6A)level was detected by methylated RIP.RESULTS SMURF1 and vascular endothelial growth factor(VEGF)were upregulated in DME.SMURF1 knockdown reduced HG/DFX-induced autophagy,which protected RPE cell tight junctions and ameliorated retinal damage in DME mice.SMURF1 activated the Wnt/β-catenin-VEGF signaling pathway by promoting WNT inhibitory factor(WIF)1 ubiquitination and degradation.IGF2BP2 upregulated SMURF1 expression in an m6A modification-dependent manner.CONCLUSION M6A-modified SMURF1 promoted WIF1 ubiquitination and degradation,which activated autophagy to inhibit RPE cell tight junctions,ultimately promoting DME progression.

Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema Correlation with variation in apparent diffusion coefficient

To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 pL shRNA- aquaporin-4 （control group） or siRNA- aquaporin-4 solution （1：800） （RNA interference group） into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25- 6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5 4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson＇s correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient （r = -0.806, P 〈 0.01）. These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracelfular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

Telmisartan Reduced Cerebral Edema by Inhibiting NLRP_3 Inflammasome in Mice with Cold Brain Injury

The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization domain（NOD）-like receptor（NLR） pyrin domain-containing 3（NLRP3） inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier（BBB） integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein（ASC） and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.

Nimodipine for treatment of perifocal edema following aspiration and drainage in patients with cerebral hemorrhage

BACKGROUND： After cephalophyma removal, perifocal edema does not disappear subsequently, but progresses occasionally. Nimodipine can improve cerebral blood flow, so it maybe reduce cerebral edema area, and speed up the absorption of edematous fluid. OBJECTIVE： To observe the effect of nimodipine on perifocal edema area and neurologic function in patients with hypertensive intracerebral hemorrhage （HICH） following stereotaxic aspiration. DESIGN： Clinical controlled observation. SETTING： Department of Neurology, Third Hospital Affiliated to Liaoning Medical University. PARTICIPANTS： Totally 116 HICH inpatients admitted to the Department of Neurology, Third Hospital Affiliated to Liaoning Medical University from January 2003 to January 2005 were involved in this experiment. They all met the classification and diagnosis of cerebrovascular disease proposed in 1995 4th National Conference on Cerebrovascular Disease. The bleeding volume ≥ 35 mL was confirmed by skull CT. The involved patients, 64 male and 52 femlae, averaged 63 years old, ranging from 40 to 70 years. All the patients suffered from unilateral cerebral hemisphere hemorrhage, and muscle strength of paralyzed limb was less than degree Ⅲ. Informed consents of therapeutic items were obtained from all the patients and relatives. METHODS： ① According to different wills, the patients were assigned into treatment group （n =60） and control group （n =56）. In the treatment group, the involved patients, 32 male, 28 female, averaged 63 years. They underwent operation and administration of nimodipine. In the control group, the involved patients, 30 male and 26 female, averaged 62 years old. They all underwent operation simply. Patients in the two groups all received stereotaxic aspiration, drainage, dehydration, haemostasis, antiinflammation, blood pressure controlling and other treatments. Patients in the treatment group were also intravenously injected with 0.2 g/L nimodipine（Bayer Medicine Health Care Co., Ltd., Lot No. 021127） at 10 mg/d. One course of treatment was 15 days. ② According to the clinical neurologic function deficit score of stroke proposed in the 4th National Conference on Cerebrovascular Disease （mild： 0-15 points; moderate： 16-30 points; severe： 31-45 points）, neurologic function deficit score and the largest perifocal edema area of patients in two groups were recorded on the 1st, 7th and 15th days after operation. The differences in perifocal edema area and neurologic deficit score between on the 1st and 7th days and between on the 7th and 15th days were calculated. MAIN OUTCOME MEASURES： Changes in the neurologic function deficit score and the largest perifocal edema area. RESULTS： Two of treatment group and 16 of control group died. Finally, 98 patients participated in the final analysis. ①In the treatment group, the difference in the largest perifocal edema area on the postoperative 7th and 15th days and on the 1st day was （1.02±0.07） and （1.86±0.10） cm2, respectively, which changed more significantly as compared with control group, respectively [（0.02±0.04）,（0.61±0.09） cm2,P 〈 0.01]. ② The difference in neurologic function deficit score between on the postoperative 15th and 1st days in the treatment group was larger than that in the control group [（7.23±0.22）,（2.68±0.32） points,P 〈 0.01]. CONCLUSION： Nimodipine obviously reduces perifocal edema area of patients with cerebral hemorrhage following aspiration and drainage, and promotes the recovery of neurologic function.

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.

Ataxia,acute mountain sickness,and high altitude cerebral edema

Previous investigations suggest that ataxia is common and often one of the most reliable warning signs of high altitude cerebral edema(HACE). The aim of this study was to investigate the diagnostic role of ataxia in acute mountain sickness(AMS)and HACE among mountain rescuers on the quake areas,and in approaching the relation between AMS and HACE. After the earthquake on April 14,2010,approximately 24 080 lowland rescuers were rapidly transported from sea level or lowlands to the mountainous rescue sites at 3 750 ~ 4 568 m,and extremely hardly worked for an emergency treatment after arrival. Assessments of acute altitude illness on the quake areas were using the Lake Louise Scoring System. 73 % of the rescuers were found to be developed AMS. The incidence of high altitude pulmonary edema(HAPE)and HACE was 0.73 % and 0.26 %,respectively,on the second to third day at altitude. Ataxia sign was measured by simple tests of coordination including a modified Romberg test. The clinical features of 62 patients with HACE were analyzed. It was found that the most frequent,serious neurological symptoms and signs were altered mental status(50/62,80.6 %)and truncal ataxia(47/62,75.8 %). Mental status change was rated slightly higher than ataxia,but ataxia occurred earlier than mental status change and other symptoms. The earliest sign of ataxia was a vague unsteadiness of gait,which may be present alone in association with or without AMS. Advanced ataxia was correlated with the AMS scores,but mild ataxia did not correlate with AMS scores at altitudes of 3 750~4 568 m. Of them,14 patients were further examined by computerized tomographic scanning of the brain and cerebral magnetic resonance imagines were examined in another 15 cases. These imaging studies indicated that the presence of the cerebral edema was in 97 % of cases who were clinically diagnosed as HACE(28/29). Ataxia seems to be a reliable sign of advanced AMS or HACE,so does altered mental status.