| Animal research has, and will undoubtedly continue to improve outcome for stroke survivors. However, controversy exists regarding the effectiveness of animal models and whether they are used properly. A survey of current ischemia studies was done to discern whether methodological procedures are improving (chapter 2). We found many rodent studies examining the efficacy of cytoprotective agents (e.g. cell saving) are lacking in many aspects (e.g., a predominance of studies assessed outcome in young male animals). One important implication is the lack of proper temperature measurement and control. Accordingly, a new method of temperature measurement that allows for continual recording via telemetry in the conscious animal is presented (chapter 3). Subsequently, two chapters examined the vulnerability of hippocampal CA1 neurons to secondary stressors (e.g., stress induced fever (SIF) due to rectal probe measurement; secondary sub-lethal transient ischemic attacks) after global ischemia in the gerbil. Rectal probe measurement causes a profound SIF that differs in ischemic and normal gerbils. Moreover, ischemic neurons salvaged by cytoprotection are susceptible to secondary ischemic insults (chapters 3 and 4 respectively).; Finally, the effects of rehabilitation after stroke were examined in two animal models of stroke. Constraint-induced movement therapy (CIMT) is used to encourage motor recovery of the hemiplegic limb in stroke patients (via immobilization of the good limb), and provides persistent benefit even when applied months after injury. However, CIMT exacerbates brain damage and reduces functional recovery in the rodent, contradicting clinical results. Post-ischemic hyperthermia potentiates ischemic injury, and was therefore examined as one potential factor in this CIMT-induced aggravation of brain injury (chapter 6). Results show CIMT causes a significant increase in brain temperature in the tissue surrounding injury, suggesting hyperthermia may, at least in part, cause potentiation of injury due to CIMT. Finally, the effects of CIMT in a rodent model of intracerebral hemorrhage (ICH) were examined. For the first time after hemorrhagic stroke in the rat, rehabilitation provided both functional and neurological recovery.; In summary, these data show a critical period of neuronal vulnerability exists in the post-lesion period, and that neurons are susceptible to a number of factors during this time. Further, these data emphasize the importance of properly monitoring and controlling these factors (e.g., temperature fluctuations) during this period, particularly in the clinic. |
