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Abstract Stroke leads to long term sensory, motor and cognitive impairments. Most patients experience some degree of spontaneous recovery which is mostly incomplete and varying greatly among individuals. The variation in recovery outcomes has been attributed to numerous factors including lesion size, corticospinal tract integrity, age, gender and race. It is well accepted that genetics play a crucial role in stroke incidence and accumulating evidence suggests that it is also a significant determinant in recovery. Among the number of genes and variations implicated in stroke recovery the val66met single nucleotide polymorphism (SNP) in the BDNF gene influences post-stroke plasticity in the most significant ways. Val66met is the most well characterized BDNF SNP and is common (40–50 % in Asian and 25–32% in Caucasian populations) in humans. It reduces activity-dependent BDNF release, dampens cortical plasticity and is implicated in numerous diseases. Earlier studies on the effects of val66met on stroke outcome and recovery presented primarily a maladaptive role. Novel findings however indicate a much more intricate interaction between val66met and stroke recovery which appears to be influenced by lesion location, post-stroke stage and age. This review will focus on the role of BDNF and val66met SNP in relation to stroke recovery and try to identify potential pathophysiologic mechanisms involved. The effects of age on val66met associated alterations in plasticity and potential consequences in terms of stroke are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists (thiazolidinediones) have anti-inflammatory effects and improve endothelium function. Here, we analyzed the effects of pioglitazone on short- and longer-term outcome after mild transient brain ischemia. 129/SV mice were subjected to 30 min filamentous middle cerebral artery occlusion (MCAo), followed by reperfusion. Post event, animals were treated with daily intraperitoneal (i.p.) pioglitazone (20 mg/kg body weight) or vehicle. Pioglitazone given acutely after transient brain ischemia/reperfusion reduced lesion size and the number of Iba1-expressing microglia in the ischemic striatum at three days. In vitro, pioglitazone attenuated migration and proliferation of primary mouse microglia. However, analysis at 6 weeks after MCAo/reperfusion no longer yielded an effect of pioglitazone on either lesion size or Iba1+ cell counts. Regarding functional longer-term outcome, we also did not detect a beneficial effect of pioglitazone on motor function measured either on the pole test or the wire hanging test or on learning and memory in the Morris water maze. Our study thus underscores the importance of extending experimental stroke studies to an analysis of longer-term outcome. [Copyright &y& Elsevier]