Role of GABA plasticity in stroke recovery

Stroke is a leading cause of long-term disability. Most stroke patients regain their function partially or fully during the first 3-6 months depending on location and size of the lesion. During this functional recovery phase, cortical reorganization or plasticity occurs, and physiological responsiveness or neuronal excitability is altered in the ipsilesional and contralesional areas. However, how to drive successful plastic changes or successful stroke recovery are not fully elucidated yet.

Activation of dopamine 2 receptors modulates glutamate decarboxylases 65 and 67 during stroke recovery in mice

Backgrounds:Treatment with levodopa enhances recovery of lost neurological functions in preclinical stroke models and patients.Here,we studied whether dopamine signaling modulates GABAergic neurotransmission in parvalbumin-positive interneurons after experimental stroke.Methods:Following block randomization,mice were subjected to experimental stroke induced by photothrombosis(PT).Two days after the insult,mice were treated either with the D1 receptor antagonist by R(+)-SCH-23390(0.1 mg/kg),the selective D1 receptor agonist(R)-(+)-SKF-38393 hydrochloride(1 mg/kg),the D2 receptor agonist R(−)-2,10,11-trihydroxy-Npropyl-noraporphine hydrobromide hydrate(TNPA)(1 mg/kg),the D2 receptor antagonist S-(−)-eticlopride hydrochloride(0.3 mg/kg),or vehicle(saline)by daily intraperitoneal injection for five consecutive days,respectively.Recovery of function was assessed by paw placement and foot fault test before and on Days 2 and 7 after surgery.Results:Mice treated with TNPA showed a statistically significant improvement of recovery compared to all other treatment conditions.Synthesis of gamma-aminobutyric acid(GABA)was quantified by levels of full-length and cleaved glutamate acid decarboxylase 67 and 65(GAD65 and GAD67)in the peri-infarct area and homotypic regions of the contralateral cortex.Compared to the other treatments,TNPA significantly reduced the level of the GAD67 isoform both in the ischemic and contralateral hemispheres.Levels of GAD65 were found significantly higher in the contralateral hemisphere in TNPA-treated mice after PT accompanied by an increase in the 58 kDa-truncated form.Conclusion:Our results point toward reduced GABA synthesis in a D2 receptor-mediated mechanism possibly contributing to counteract functional inhibition after stroke.

Reactive astrocytes promote axonal remodeling and neurological recovery after stroke

Stroke is a leading cause of death and disability in adults worldwide. For decades, the primary approach and goal of therapy for stroke has focused on neuroprotection, namely treating the injured tissue, with interventions designed to reduce the volume of cerebral infarction. Enormous effort in the laboratory has been devoted to the development of neuroprotective agents in an attempt to salvage ischemic neurons in the brain from irreversible injury; however, all these efforts have failed to demonstrate efficacy in clinical trials of stroke. In order to treat stroke, we have to re-con- ceptualize and redefine our therapeutic targets. Acute neu- roprotective treatments for stroke fight a temporal battle of salvaging cerebral tissue before the onset of death, as well as a physiological impediment of delivery of therapy to tissue which has inadequate blood flow.

Changes in cortical activation patterns accompanying somatosensory recovery in a stroke patient: a functional magnetic resonance imaging study

The somatosensory system plays a crucial role in executing precise movements by providing sensory feedback （Farrer et al., 2003; Rabin and Gordon, 2004）. Somatosensory dys- function is a common problem following stroke. In partic- ular, somatosensory impairments, such as impairment in touch, proprioception, light touch, and vibration have been frequently observed （Carey et al., 1993; Sullivan and Hed- man, 2008; Tyson et al., 2008）. Patients with somatosensory dysfunction show negative effects on motor control, and it sometimes becomes difficult to perform daily activities independently.

Evaluation of the Curative Effect of "Xingnao Kaiqiao" Acupuncture Based on Brunnstrom Staging on Upper Limb and Hand Motor Function in the Recovery Period after Stroke

Objective: To observe the effects of Xingnao Kaiqiao acupuncture(醒脑开窍针) on the motor function of upper limb and hand in the recovery period after stroke. Methods: Seventy-six cases of hemiplegia patients with ischemic stroke were divided into the treatment group and the control group(n=38 in each). Based on the Brunnstrom's stage of Xingnao Kaiqiao acupuncture combined with rehabilitation training was used in the treatment group, and the control group was given rehabilitation training. FuglMeyer Assessment of the upper extremity(FMA-UE), Action Research Arm Test(ARAT) and Simple Test for Evaluating hand Function(STEF) were adopted separately to compare scores before treatment and 8 weeks after treatment. Results: The difference was not statistically significant in the two groups of patients for comparison of FMA-UE, ARAT and STEF scores before treatment(P>0.05). The difference was statistically significant in the two groups of score comparison of FMA-UE, ARAT and STEF after treatment(P<0.05). Conclusion: The Xingnao Kaiqiao acupuncture has its unique advantages in improving recovery of motor function of upper limb and hand in recovery period after stroke.

Effect of early recovery training on motor function's recovery in stroke patients

Objective To observe theeffectof early recovery trainingonmotorfunctioninstrokepatients.Method118casessufferingfromcerebralapoplexywererandomlydividedintotwogroupsrehabilitationgroup59casescontrastgroup59cases.Theformertooktheearlyrecoverytrainingandthelattertooktheroutinetreatment.ResultAfterthetreatmenttheformer’scurativeeffectwasbetterthanthelatterandtheirdyskinesiaturnedforthebetterobviously.ConclusionTheearlyrecoverytrainingcandecreasethecripplingrateinstrokepatients.

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

This study investigated whether bone marrow mesenchymal stem cell（BMSC） transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs（h BMSCs） were injected into the tail vein. Fourteen days later, we found that h BMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor（s EPOR） was injected into the lateral ventricle, and on the next 13 consecutive days. s EPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the h BMSCs ＋ s EPOR group than in the h BMSCs ＋ heat-denatured s EPOR group. The adhesive-removal test result and the modified Neurological Severity Scores（m NSS） were lower in the h BMSCs ＋ s EPOR group than in the heat-denatured s EPOR group. The adhesive-removal test result and m NSS were similar between the h BMSCs ＋ heat-denatured s EPOR group and the h BMSCs ＋ s EPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.