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Traumatic brain injury (TBI) is a major cause of chronic disability. Worldwide, it is the leading cause of disability in the under 40s. Behavioral problems, mood, cognition, particularly memory, attention, and executive function are commonly impaired by TBI. Spending to assist, TBI survivors with disabilities are estimated to be costly per year. Such impaired functional outcomes following TBI can be improved via various rehabilitative approaches. The objective of the present paper is to review the current rehabilitation treatment of traumatic brain injury in adults.

Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms. To date, the relation between melatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models. This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH. Adult male SD rats were divided into four groups: (i) control group (n = 18); (ii) SAH group (n = 18); (iii) SAH + vehicle group (n = 18); and (iv) SAH + melatonin group (n = 18). The rat SAH model was induced by injection of 0.3 mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20 s. In SAH + melatonin group, melatonin was administered i.p. at 150 mg/kg at 2 and 24 hr after the induction of SAH. Brain samples were extracted at 48 hr after SAH. Treatment with melatonin markedly increased the expressions of Nrf2-ARE pathway-related agents, such as Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase α-1. Administration of melatonin following SAH significantly ameliorated EBI, including brain edema, blood–brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In conclusion, post-SAH melatonin administration may attenuate EBI in this SAH model, possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes.

Cyclophilin A has been found to be involved in many inflammatory diseases via its receptor, cluster of differentiation 147 (CD147). This study was designed to estimate the potential role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury.Controlled in vivo laboratory study.Animal research laboratory.Two hundred ninety adult male Sprague-Dawley rats weighing 300-350 g.A prechiasmatic cistern single-injection model was used to produce experimental subarachnoid hemorrhage in Sprague-Dawley rats. The expressions of cyclophilin A and CD147, the interaction between cyclophilin A and CD147, and the secretion of cyclophilin A were assessed using immunofluorescence staining, Western blot analysis, and coimmunoprecipitation analysis. Down-regulation of cyclophilin A expression by small interfering RNA was performed, and recombinant human cyclophilin A and monoclonal antibody of CD147 were exploited to study the role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury.The expressions of cyclophilin A and CD147 in neurons were higher than that of the sham group and peaked at 24 hours after subarachnoid hemorrhage. Compared with sham group, subarachnoid hemorrhage was found to increase the secretion of cyclophilin A and the interaction between cyclophilin A and CD147. Cyclophilin A small interfering RNA and anti-CD147 treatments were found to ameliorate subarachnoid hemorrhage-induced early brain injury, including cortical apoptosis and necrosis, brain edema, blood-brain barrier damage, and neurobehavioral deficits. Cyclophilin A small interfering RNA and anti-CD147 treatments also decreased the phosphorylation of extracellular signal-regulated protein kinase 1/2, the protein levels of p53 and caspase-3, and the level of active nuclear factor-κB. Finally, recombinant human cyclophilin A treatment resulted in an opposite effect, which was inhibited by anti-CD147 treatment.Cyclophilin A/CD147 interactions may participate in subarachnoid hemorrhage-induced early brain injury via increasing neuronal apoptosis pathway, at least partly through the ERK1/2-nuclear factor-κB pathway. Cyclophilin A/CD147 may be a suitable therapeutic target for subarachnoid hemorrhage.

Background Cerebral hemorrhagic stroke, including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and hemorrhagic transformation after cerebral infarction, is a major medical emergency in the neurology, neurosurgery, emergency and other clinical departments. The pathophysiological mechanisms of these cerebral hemorrhagic diseases have not been fully elucidated, and there are no effective pharmacological and molecular treatments against these diseases. Matrix metalloproteinase-9 (MMP-9), also known as collagenase B, is one of the most important members of the matrix metalloproteinases (MMPs) family. Objective This article reviews the role of MMP-9 in the pathogenesis of diseases such as brain hemorrhage, hemorrhagic transformation after cerebral infarction, SAH, and brain injury. Results The expression levels of MMP-9 in brain tissue increased after cerebral hemorrhage and related to the prognosis of brain hemorrhage. MMP-9 is related to post-thrombolytic hemorrhagic transformation after cerebral infarction. Inhibition of MMP-9 can reduce secondary brain injury after brain hemorrhage. MMP-9 aggravates the early brain injury and cerebral vasospasm after SAH. Conclusion MMP-9 is involved in the pathological process of hemorrhagic stroke through a variety of mechanisms and is closely related to prognosis after cerebral hemorrhagic stroke.

This study investigated the possible involvement of matrix metalloproteinase 9 (MMP-9) in cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rats. The CVS model was established by injection of fresh autologous nonheparinized arterial blood into the cisterna magna. Experiment 1 aimed to investigate the timecourse of the MMP-9 expression in the basilar artery after SAH. In Experiment 2, we chose the maximum time point of vasospasm (Day 3) and assessed the effect of SB-3CT (a selective MMP- 9 inhibitor) on the regulation of cerebral vasospasm. The cross-sectional area of basilar artery was measured by HE staining and the MMP-9 expression was assessed by immunohistochemistry analysis. The elevated expression of MMP-9 was detected in the basilar artery after SAH and peaked on day 3. After intracisternal administration of SB-3CT, the vasospasm was markedly attenuated after blood injection on day 3. Our results suggest that MMP-9 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in this rat experimental model of SAH and that the administration of the specific MMP-9 inhibitor could prevent or reduce cerebral vasospasm caused by SAH.

Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms. To date, the relation between melatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models. This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH. Adult male SD rats were divided into four groups: (i) control group (n=18); (ii) SAH group (n=18); (iii) SAH+vehicle group (n=18); and (iv) SAH+melatonin group (n=18). The rat SAH model was induced by injection of 0.3mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20s. In SAH+melatonin group, melatonin was administered i.p. at 150mg/kg at 2 and 24hr after the induction of SAH. Brain samples were extracted at 48hr after SAH. Treatment with melatonin markedly increased the expressions of Nrf2-ARE pathway-related agents, such as Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase α-1. Administration of melatonin following SAH significantly ameliorated EBI, including brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In conclusion, post-SAH melatonin administration may attenuate EBI in this SAH model, possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes.

Is a common feature of progressive renal diseases regardless of the initiating insult To clarify the role of connective tissue growth factor (CTGF) in after (UUO) in renal interstitial fibrosis and effects of rapamycin (RAP) thereupon.Eighteen Sprague-Dawley rats were randomly divided into 3 equal groups: unilateral ureteral obstruction (UUO) model group, undergoing ligation of the left ureter; RAP treatment group, undergoing ligation of the left ureter and intraperitoneal injection of RAP 0.04 mg.kg(-1).d(-1); and sham operation group. The right kidneys were taken out 7 and 14 days after the operation respectively to undergo renal pathological examination by Masson staining. Semi-quantitative RT-PCR was used to detect the mRNA expression of CTGF. Western blotting was performed to examine the protein expression of CTGF and fibronectin (FN).In comparison with the sham operation group, renal interstitial fibrosis was significant more expression in the 2 UUO groups, especially the UUO model group (P0.01). Seven and 14 days after the operation the levels of CTGF mRNA expression of the UUO model and RAP treatment groups (both P0.01), and the level of CTGF mRNA expression of the RAP treatment group was significantly lower than that of the UUO model group (P0.01), however, there was no significant difference in the level of CTGF mRNA expression between the 2 UUO groups 14 days after the operation. Seven and 14 days after the operation the levels of CTGF protein expression of the UUO model and RAP treatment groups were both significantly higher than that of the sham operation group (both P0.01), and the levels of CTGF protein expression of the RAP treatment group were significantly lower than that of the UUO model group (P0.05 and P0.01). The levels of FN expression 7 and 14 days after the operation of the 2 UUO groups were both significantly higher than that of the sham operation group (both P0.01). and the level of FN expression 7 days after of the RAP treatment group was significantly lower than that of the UUO model group (P0.01), however, there was no significant difference in the level of FN expression between the 2 UUO groups 14 days after the operation.The expression of CTGF mRNA and that of CTGF protein increase after UUO. Rapamycin play a protective role in the kidney by downregulating the CTGF expression and alleviating the renal interstitial fibrosis following UUO.