Efficacy of acupuncture in experimental intracerebral hemorrhage: a systematic review and meta-analysis.

Objective: There is currently a lack of evidence in evidence-based medicine regarding acupuncture treatment for experimental intracerebral hemorrhage (ICH). The aim of this study was to systematically evaluate the efficacy of acupuncture treatment for experimental ICH based on neurological function scores and brain water content (BWC). Methods: Eight mainstream Chinese and English databases were searched. Outcome measures included neurological function scores and BWC, and subgroup analysis was conducted based on study characteristics. Results: A total of 32 studies were included. Meta-analysis results indicated that compared to the control group, the acupuncture group showed significant reductions in mNSS (MD = -3.16, p < 0.00001), Bederson score (MD = -0.99, p < 0.00001), Longa score (MD = -0.54, p < 0.0001), and brain water content (MD = -5.39, p < 0.00001). Subgroup analysis revealed that for mNSS, the autologous blood model (MD = -3.36) yielded better results than the collagenase model (MD = -0.92, p < 0.00001), and simple fixation (MD = -3.38) or no fixation (MD = -3.39) was superior to sham acupuncture (MD = -0.92, p < 0.00001). For BWC, the autologous blood model (MD = -7.73) outperformed the collagenase model (MD = -2.76, p < 0.00001), and GV20-GB7 (MD = -7.27) was more effective than other acupuncture points (MD = -2.92, p = 0.0006). Conclusion: Acupuncture significantly improves neurological deficits and brain edema in experimental ICH. Acupuncture at GV20 - GB7 is more effective than at other points. These findings support further studies to translate acupuncture into clinical treatment for human ICH. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023435584.

Lessons on brain edema in HE: from cellular to animal models and clinical studies.

Brain edema is considered as a common feature associated with hepatic encephalopathy (HE). However, its central role as cause or consequence of HE and its implication in the development of the neurological alterations linked to HE are still under debate. It is now well accepted that type A and type C HE are biologically and clinically different, leading to different manifestations of brain edema. As a result, the findings on brain edema/swelling in type C HE are variable and sometimes controversial. In the light of the changing natural history of liver disease, better description of the clinical trajectory of cirrhosis and understanding of molecular mechanisms of HE, and the role of brain edema as a central component in the pathogenesis of HE is revisited in the current review. Furthermore, this review highlights the main techniques to measure brain edema and their advantages/disadvantages together with an in-depth description of the main ex-vivo/in-vivo findings using cell cultures, animal models and humans with HE. These findings are instrumental in elucidating the role of brain edema in HE and also in designing new multimodal studies by performing in-vivo combined with ex-vivo experiments for a better characterization of brain edema longitudinally and of its role in HE, especially in type C HE where water content changes are small.

Brain water content in sudden unexpected infant death.

The extensive and rapid development of the human brain during the first years of life complicates the postmortem diagnosis of brain edema in infancy. The aim of this study was to describe brain water content, the brain weight/body weight ratio, and the brain weight/head circumference ratio throughout the first years of life. Furthermore, we examined the relationship between these parameters and rs2075575 in the AQP4 gene. Our hypothesis was that dysregulated water homeostasis might be a risk factor for sudden infant death syndrome (SIDS), which may be reflected by increased water content in the brain. The study included 90 subjects with sudden unexpected death < 4 years of age: 22 cases of sudden infant death syndrome, 11 cases of sudden unexplained death in childhood, 47 cases of death due to disease, and 10 cases of accident/violent death. Brain water content, brain weight/body weight ratio, and brain weight/head circumference ratio were investigated according to corrected age, diagnosis group, attempt to resuscitate, and presence of brain edema. We found that brain water content and brain weight/body weight ratio were significantly reduced with increasing age, while brain weight/head circumference were increased. Brain weight/head circumference was correlated with brain water content. Cases with brain edema had a significantly higher brain weight/head circumference than the non-edematous cases. No differences were found between the diagnosis groups for any of the investigated parameters. In summary, the findings contribute to the current body of knowledge regarding brain growth during the first months of life.

Meprin ß: A novel regulator of blood-brain barrier integrity.

The metalloprotease meprin ß (Mep1b) is capable of cleaving cell-adhesion molecules in different tissues (e.g. skin, kidney and intestine) and is dysregulated in several diseases associated with barrier breakdown (Alzheimer´s disease, kidney disruption, inflammatory bowel disease). In this study, we demonstrate that Mep1b is a novel regulator of tight junction (TJ) composition and blood-brain barrier (BBB) integrity in brain endothelium. In Mep1b-transfected mouse brain endothelial cells (bEnd.3), we observed a reduction of the TJ protein claudin-5, decreased transendothelial electrical resistance (TEER) and an elevated permeability to paracellular diffusion marker [14C]-inulin. Analysis of global Mep1b knock-out (Mep1b-/-) mice showed increased TJ protein expression (claudin-5, occludin, ZO-1) in cerebral microvessels and increased TEER in cultivated primary mouse brain endothelial compared to wild-type (wt) mice. Furthermore, we investigated the IgG levels in cerebrospinal fluid (CSF) and the brain water content as additional permeability markers and detected lower IgG levels and reduced brain water content in Mep1b-/- mice compared to wt mice. Showing opposing features in overexpression and knock-out, we conclude that Mep1b plays a role in regulating brain endothelial TJ-proteins and therefore affecting BBB tightness in vitro and in vivo.

Protective effect of hypoxia inducible factor-1α gene therapy using recombinant adenovirus in cerebral ischaemia-reperfusion injuries in rats.

Context: Hypoxia-inducible factor-1α (HIF-1α)-induced genes can improve blood circulation.Objective: To investigate brain protective effect of recombinant adenovirus-mediated HIF-1α (AdHIF-1α) expression and its mechanism.Materials and methods: Male SD rats were used to establish focal cerebral ischaemia-reperfusion (CIR) injury models and randomly divided into normal, sham, CIR, Ad and AdHIF-1α groups. Ad or AdHIF-1α (108 pfu/10 µL) were administered into lateral ventricle of rats in Ad and AdHIF-1α groups. Modified neurological severity score (mNSS), brain water content (BWC) and cerebral infarct volumes (CIVs) were analyzed, and HE staining was performed using the brain tissues. Furthermore, the expression of caspase-3 and HSP90 was analyzed using qRT-PCR and Western blotting.Results: Compared to CIR (mNSS, 8.52 ± 0.52; CIV, 0.22 ± 0.01) and Ad groups (mNSS, 8.83 ± 0.41; CIV, 0.22 ± 0.02), mNSS and CIV were significantly decreased in AdHIF-1α group (mNSS, 6.03 ± 0.61; CIV, 0.11 ± 0.01) at 72 h (p < 0.05). With prolonged reperfusion time (6 h to 72 h), BWC of all rats increased gradually, although the increase was markedly less in AdHIF-1α group (78.15 ± 0.16 to 87.01 ± 0.31) compared to that in CIR (78.77 ± 0.60 to 89.74 ± 0.34) and Ad groups (78.77 ± 0.35 to 89.71 ± 0.27) (p < 0.01). There were significantly greater pathological changes in the neurons in AdHIF-1α group at 72 h following CIR. Furthermore, expression of caspase-3 (p < 0.01) down-regulated and HSP90 up-regulated (p < 0.05) at mRNA and protein levels in AdHIF-1α group.Discussion and conclusions: HIF­1α gene therapy is neuroprotective towards the CIR rat model. HIF-1α may be a candidate gene for the treatment of ischaemic brain injury.

Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage.

Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms. In this study, a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats. Z-IETD-FMK (0.5, 1, 2 mg/kg; an inhibitor of caspase-8) was delivered via intravenous (tail vein) injection immediately after subarachnoid hemorrhage. After 12 hours of subarachnoid hemorrhage, western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours, peaked at 24 hours, and then decreased at 72 hours after subarachnoid hemorrhage. Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage. Z-IETD-FMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage. The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21-27 days after subarachnoid hemorrhage. Furthermore, inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3, caspase-1, and interleukin-1ß after subarachnoid hemorrhage. In conclusion, our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University, China (approval No. 2016-193) on February 25, 2016.

Protective effect of human umbilical cord blood mesenchymal stem cells on the rat’s blood-brain barrier after traumatic brain injury / 中国组织工程研究

BACKGROUND: Human umbilical cord mesenchymal stem cells play a vital role in the repair of the blood-brain barrier after traumatic brain injury. OBJECTIVE: To investigate the protective effect of human umbilical cord blood mesenchymal stem cell transplantation on the blood-brain barrier after traumatic brain injury in rats and its possible mechanism. METHODS: Sixty Sprague-Dawley rats were randomly divided into sham operation group, injury control group (model group), cell transplantation group and Sunitinib group, with 15 rats in each group. Traumatic brain injury model was established by improved hydraulic impact method in all the groups except for the sham operation group. Rats in the sham operation group and model group were injected with 1 mL of normal saline, and those in the cell transplantation group were injected with 1 mL of 2×109/L human umbilical cord blood mesenchymal stem cells. The injection was done via the tail vein at 0.5, 24, and 48 hours after modeling. In the Sunitinib inhibitor group, the rats were given oral PDGFR-β pathway inhibitor, Sunitinib (80 mg/kg), from 1 day before modeling until being executed. Three days after modeling, the water content in brain tissue was measured by dry-wet specific gravity method, the permeability of the blood-brain barrier was measured by Evans blue method, expression of GFAP and vWF was observed by immunofluorescence staining and the expression of blood-brain barrier related proteins and PDGFR-β pathway proteins was detected by western blot method. RESULTS AND CONCLUSION: Compared with the sham operation group, the brain water content of the model group increased significantly (P < 0.05), while that of the cell transplantation group was significantly lower than that of the model group (P < 0.05). The Evans blue content in the model group was significantly higher than that in the sham operation group (P < 0.05), while the Evans blue content in the cell transplantation group was significantly lower than that in the model group (P < 0.05). Compared with the sham operation group, the expression of vWF and GFAP increased significantly in the model group (P < 0.05), while compared with the model group, the expression was significantly reduced in the cell transplantation group (P < 0.05). Western blot showed that ZO-1, Oclaudin-5, and PDGFR-β protein expressions in the model group were significantly lower than those in the sham operation group (P < 0.05), while these expressions were significantly increased in the cell transplantation group as compared with the model group (P < 0.05). To conclude, intravenous injection of human umbilical cord mesenchymal stem cells through the tail ein can reduce the permeability of blood-brain barrier and play a neuroprotective role in rats with traumatic brain injury. Its possible mechanism is related to the promotion of PDGFR-β expression in the injured area.

Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway.

BACKGROUND: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. OBJECTIVE: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. METHODS: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. RESULTS: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. CONCLUSION: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.

Effects of Increased Intracranial Pressure Gradient on Cerebral Venous Infarction in Rabbits.

BACKGROUND: Cerebral venous infarction (CVI) is a rare vascular disease most commonly caused by cerebral venous thrombosis that leads to hemorrhage or infarct formation. A rabbit model of CVI was established by placing a recoverable epidural sacculus to research effects of increased pressure on CVI. METHODS: Rabbits were randomly divided into the following groups: A, CVI; B, 0.2-mL epidural sacculus placed on the basis of CVI; C, 0.4-mL epidural sacculus; D, 0.6-mL epidural sacculus; E, sham operation. Two sacculus-release groups were then added, 8 hours (group F) and 24 hours (group G), on the basis of group D. Brain water content, extent of cerebral infarction, hemorheology indexes, D dimer, and fibrinogen were observed at 8, 24, and 48 hours after surgery. RESULTS: Brain water content was higher in groups A-D compared with group E with the exception of the 24-hour A group. Brain water content was significantly lower in sacculus-release groups compared with the 48-hour D group. Extent of cerebral infarction in group D was significantly higher at 24 and 48 hours compared with groups A and E. Extent of cerebral infarction in sacculus-release groups was significantly lower compared with group D at 48 hours. Hemorheology indexes and fibrinogen were significantly higher in group D compared with groups A and E at corresponding time points and increased with increasing intracranial pressure. CONCLUSIONS: In the rabbit model of CVI, degree of brain edema, extent of cerebral infarction, hemorheology indexes, and fibrinogen increased as intracranial pressure gradient increased, which may promote formation of a hypercoagulable state. Early removal of intracranial hypertension reduced degree of edema and extent of cerebral infarction in rabbits.

Therapeutic effect of transplantation of ApoJ-modified bone marrow mesenchymal stem cells on intracere-bral hemorrhage in rats and its action mechanism / 医学研究生学报

Objective The nerve-protective effect of Apoli-poprotein J ( ApoJ) in intracerebral hemorrhage ( ICH) is not yet clarified.This study aimed to explore the therapeutic effect of trans -plantation of bone marrow mesenchymal stem cells (BMSCs) carrying the ApoJ gene on intracerebral hemorrhage in rats and its possible ac -tion mechanism. Methods Rat BMSCs were isolated, cultured in vitro, and transfected with the recombinant plasmid pEGFP -N1-ApoJ mediated with lipofectamine.Ninety-six SD rats were randomly divided into groups A, B and C, and ICH models were established by two -step autologous intracranial blood injection .At 24 hours after model-ing, the rats in groups A, B, and C were transplanted with the same volume of ApoJ-transfected BMSC suspension, BMSC suspension and normal saline, respectively.At 1, 3, 5 and 7 days after transplantation, the neurofunction recovery of the rats were evaluated with modified Neurological Severity Scores (mNSS), the brain water content measured by the dry -wet weight method, and the expression level of complement component 3 (C3) in the brain tissue detected by Western blot . Results The mNSS exhibited no statistically significant differences among the three group of rats on the 1st day after transplantation (P>0.05), but was remarkably lower in group A than in B and C on the 3rd (8.13±0.99 vs 9.25±1.28 and 10.88±0.84, P<0.05), 5th (6.75±1.04 vs 8.50±1.41 and 9.75±0.89, P<0.05) and 7th day (5.63±0.52 vs 7.00±0.54 and 7.88±1.25, P<0.05), and markedly lower in group B than in C (P<0.05).The water content in the brain tissue was also significantly lower in group A than in B and C on the 1st (78.17±0.82 vs 78.83±0.56 and 80.38±0.35, P<0.05), 3rd (78.68±0.55 vs 79.12±0.26 and 81.47±0.26, P<0.05), 5th (77.00±0.58 vs 78.13±0.46 and 79.74± 0.41, P<0.05) and 7th day (75.89±0.46 vs 76.86±0.29 and 78.44±0.44, P<0.05), and remarkably lower in group B than in C (P<0.05).Western blot showed that the expression of the C 3 protein in the brain tissue was markedly decreased in group A as compared with B and C on the 1st (0.096±0.011 vs 0.212±0.014 and 0.440±0.006, P<0.05), 3rd (0.083±0.005 vs 0.164±0.013 and 0.604± 0.011, P<0.05), 5th (0.064±0.009 vs 0.105±0.010 and 0.333±0.010, P<0.05), 7th day (0.045±0.007 vs 0.091±0.004 and 0.141± 0.003, P<0.05), and significantly lower in group B than in C (P<0.05). Conclusion ApoJ can promote the recovery of the neuro-logical function of ICH rats by inhibiting complement activation -mediated secondary brain damage and alleviating cerebral edema .

Role of flunarizine hydrochloride in secondary brain injury following intracerebral hemorrhage in rats.

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.

Comparison of speed-vacuum method and heat-drying method to measure brain water content of small brain samples.

BACKGROUND: A reliable measurement of brain water content (wet-to-dry ratio) is an important prerequisite for conducting research on mechanisms of brain edema formation. The conventionally used oven-drying method suffers from several limitations, especially in small samples. A technically demanding and time-consuming alternative is freeze-drying. NEW METHOD: Centrifugal vacuum concentrators (e.g. SpeedVac/speed-vacuum drying) are a combination of vacuum-drying and centrifugation, used to reduce the boiling temperature. These concentrators have the key advantages of improving the freeze-drying speed and maintaining the integrity of dried samples, thus, allowing e.g. DNA analyses. In the present study, we compared the heat-oven with speed-vacuum technique with regard to efficacy to remove moisture from water and brain samples and their effectiveness to distinguish treatment paradigms after experimental traumatic brain injury (TBI) caused by controlled cortical impact (CCI). RESULTS: Both techniques effectively removed water, the oven technique taking 24h and vacuum-drying taking 48h. Vacuum-drying showed lower variations in small samples (30-45mg) and was suitable for genomic analysis as exemplified by sex genotyping. The effect of sodium bicarbonate (NaBic8.4%) on brain edema formation after CCI was investigated in small samples (2×1mm). Only vacuum-drying showed low variation and significant improvement under NaBic8.4% treatment. COMPARISON WITH AN EXISTING METHOD: The receiver operating curves (ROC) analysis demonstrated that vacuum-drying (area under the curve (AUC):0.867-0.967) was superior to the conventional heat-drying method (AUC:0.367-0.567). CONCLUSIONS: The vacuum method is superior in terms of quantifying water content in small samples. In addition, vacuum-dried samples can also be used for subsequent analyses, e.g., PCR analysis.

Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats.

Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.

Regional cerebral blood flow and cellular environment in subarachnoid hemorrhage: A thermal doppler flowmetry and microdialysis study.

BACKGROUND: Cerebral microdialysis enables assessment of regional metabolic physiology and provides biomarkers for clinical correlation in critical conditions, such as subarachnoid hemorrhage (SAH). The aim of our current study was to investigate the correlation between regional cerebral blood flow and microdialysis parameters (glucose, lactate, glycerol, pyruvate concentrations, and lactate/pyruvate metabolic ratio) in patients with SAH. MATERIALS AND METHODS: Twenty-one patients with SAH were enrolled in our retrospective study. Cerebral blood flow (CBF) based on thermal diffusion methodology, the thermal coefficient K, and microdialysis biochemical markers were recorded. The duration of the brain monitoring was 10 days. RESULTS: Microdialysis glucose concentration was inversely related to the cerebral temperature and to the L/P ratio. Furthermore, it was positively correlated to all other microdialysis parameters but glycerol. The K coefficient was strongly and positively correlated with the temperature and marginally with the CBF. The L/P ratio was positively correlated with glycerol, while it was inversely correlated with the CBF. Patients who died had elevated L/P ratio and K coefficient compared to the survivors in our series. CONCLUSIONS: Thermal conductivity coefficient may change over time as cerebral injury progresses and tissue properties alter. These alterations were found to be associated with the microdialysis metabolite concentrations and the CBF itself. The microdialysis biochemical indices of cell stress and death (glycerol, L/P ratio) were positively related to each other, while the measured L/P metabolic ratio was higher among patients who died.

Minimally invasive surgery for removing intracranial hematoma and decreasing perihematomal glutamate content and permeability of blood-brain barrier / 重庆医学

Objective To investigate the effects of minimally invasive intracranial hematoma clearance on the perihematomal glutamate(Glu) level,permeability of blood-brain barrier(BBB) and brain edema.Methods Thirty rabbits with body weight of 2.80-3.40 kg were used to established the model of spontaneous intracerebral hemorrhage(ICH) and randomly divided into the minimally invasive group(MI) and control group(MC) after the model was prepared successfully.The MI group underwent minimally invasive procedures for removing intracranial hematoma by stereotactic instrument within 6 h after establishing the ICH model.The brain tissue was extracted on postoperative 1,3,7 d,and the perihematomal brain tissues were taken to detect the Glu level,BBB permeability and water content of brain tissue,which were compared with those in the control group.Results The Glu level,BBB permeability and brain water content on 1,3,7 d in the MI group were lower than those in the MC group,and the differences were statistically significant(P＜0.05).Conclusion The minimally invasive surgery for removing intracranial hematoma is helpful to reduce perihematoma Glu level,BBB permeability and brain water content.

Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury.

The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect.

Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury.

Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 µL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

Covert hepatic encephalopathy: elevated total glutathione and absence of brain water content changes.

Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local brain water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy ((1)H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI brain water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with brain water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.

Protective effects of Sparstolonin B on mouse with intracerebral haemorrhage / 中国药学杂志

OBJECTIVE: To study the protective effects of sparstolonin B(8,5'-dihydroxy-4-phenyl-5,2'-oxidoisocoumarin, SsnB) on mouse with intracerebral haemorrhage (ICH). METHODS: The effect of SsnB on neuronal cell death induced by Hb using a microglia-neuron transwell system was investigated. Autologous nonanticoagulated blood was collected from the tail artery of the mouse and then injected into the striatum using a syringe pump. Neurological deficit of the mouse with ICH was assessed 1,3,5 and 7 d after SsnB administration using modified neurological severity score system, and brain water content of the mouse cerebral tissues after ICH was measured at the same day. The concentrations of pro-inflammatory cytokines in perihematoma tissues, including interleukin-6, interleukin-1 p and tumor necrosis factor-α, were measured by ELISA assay. RESULTS: The results show that SsnB significantly reduced the neurological deficit scores and the brain water content, and inhibited the levels of IL-6, IL-1β and TNF-α at first day and third day after ICH. CONCLUSION: SsnB can improve the brain injury in mouse induced by ICH. The mechanism may involve increased the neuronal survival rate and decreased expression of pro-inflammatory cytokines of mouse after ICH.

Dual-porosity poroviscoelasticity and quantitative hydromechanical characterization of the brain tissue with experimental hydrocephalus data.

Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging. This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot's theory of poroviscoelasticity, and adopts the generalized Kelvin's rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space. Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow-up perfusion of cats' brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data. The convoluted and coupled solution results are presented through the time-dependent plots of the ventricular volume undergoing the perfusion experiment. The plots demonstrate the intricate interplay of viscous and poroelastic diffusive time scales, and their competition in reaching the steady state response of the system.