The aim was to study if exposure to an enriched environment influenced graft-host interface and neuronal markers in neocortical grafts implanted in cortical infarct cavities 3 weeks after distal ligation of the middle cerebral artery in adult hypertensive rats. Half the rats were exposed to an enriched environment for 2h daily 5 days a week starting 1 week after the arterial ligation. The brain was fixed by perfusion 4 weeks postgrafting. The immunoreactivity to glial fibrillary acidic protein, microtubule associated protein 2, and synaptophysin was studied in coronal paraffin-embedded sections. A distinct glial border separated the infarct cavity from the surrounding brain in sham-transplanted rats. Most grafts filled the larger part of the infarct cavity. In 8 of 18 transplants, 4 in each experimental group, part of the transplants protruded through the thin glial membrane that delineated the transplant-host interface into the adjacent host brain tissue. Microtubule associated protein 2 immunostained sections indicated bridging of dendrites in the host-transplant interface. Synaptophysin immunoreactivity was significantly higher in grafts than in contralateral cortex. However, graft morphology and neuronal marker immunoreactivity did not differ between rats housed in standard and activity stimulating cages.

Background and Purpose-The cerebrovascular lesions in stroke-prone spontaneously hypertensive rats are not only dependent on high blood pressure but partly related to pressure-independent genetic factors. The aim of the present study was to observe whether spontaneous stroke occurred in renovascular hypertensive rats without a genetic deficiency. Methods-The 1-kidney, 1 clip (1k1c); 2-kidney, 1 clip (2k1c); and 2-kidney, 2 clip (2k2c) methods were used to induce hypertension in male Sprague-Dawley rats with a ring-shaped silver clip. Sham-operated rats were used as controls. Blood pressure and neurological symptoms were observed in the rats without any artificial inducement. Brain sections stained with hematoxylin-eosin and phosphotungstic acid-hematoxylin were examined under a microscope to determine stroke foci. Results—The attack rate of stable hypertension was 100% (55/55) in the 2k2c group, which was significantly higher than that in the 1k1c (23/30, 76.7%) and 2k1c (21/30, 70%) groups (P,0.01). None of the rats in the 2k2c group died of acute renal failure or suffered from diffuse cerebral lesions postoperatively. Forty weeks after renal artery constriction, the incidence of spontaneous stroke in the 2k2c group was 61.8% (34/55), which was significant higher than that in the 1k1c (7/30, 23.3%) and 2k1c (5/30,16.7%) groups (P,0.01). Stroke foci were not observed in normotensive controls.Conclusions-We conclude that 2k2c renovascular hypertensive rats with proper renal artery constriction can be used as stroke-prone renovascular hypertensive rats independent of a genetic deficiency. (Stroke. 1998; 29:1708-1714.)

Early overuse of a lesioned forelimb, induced by immediate immobilization of the intact forelimb after a cortical lesion, has been reported to increase tissue damage and delay functional recovery. To investigate if early training without immobilization of the intact forelimb could increase tissue loss and reduce recovery, the middle cerebral artery was ligated distal to the striatal branches in 25 male spontaneously hypertensive rats. Control rats were housed in standard cages, training rats were transferred to larger cages allowing various activities and received additional special training 1 hour a day starting either 24 hours or 7 days after the ligation. The rats were tested on a rotating pole, in a leg placement test, and in a water maze and they were killed 6 weeks after the ligation. Delayed training resulted in the best overall performance; however, both training groups performed better than standard rats on the rotating pole. The cortical infarct volume was larger in the early training group than in the other two groups (P<.005), possibly related to increased glutamate release and peri-infarct cortical hyperexcitability.

Zinc-positive neurons and terminals, known to be associated with the glutamatergic projections in the brain, can be demonstrated by the histochemical Timm method and later modifications thereof. The adult rat neocortex contain a uniform lamination of zinc-positive cells with specific projections to, e.g., the striatum. We have previously reported that fetal neocortical grafts implanted in the adult rat neocortex combined with rearing in an enriched environment can improve behavioral functions and reduce the secondary atrophy of thalamus after cortex infarction in adult rats. In order to examine whether the expression of zinc positivity is ontogenetically inherent to neocortical neurons we grafted fetal neocortical tissue to aspiration or ischemic lesions of the frontoparietal neocortex of adult rats, followed by histochemical visualization of the vesicular zinc pool by selenite or sulfide. One further aim of the study was to elucidate to what extent the distribution of zinc-containing neurons and terminals in the grafts depended on rearing under different environmental conditions. The foremost finding of the present study was that the overall density of zinc-containing terminals in fetal cortical transplants placed in brain infarcts of adult spontaneously hypertensive rats is higher when the rats are reared in an enriched environment. Moreover, the presence and expression of zinc-positive neurons and terminals do not seem to be ontogenetically inherent to the cortical neurons as the fetal neocortical grafts placed in aspiration lesions contained no zinc-selenide-positive neurons and few or no zinc-selenide-positive terminals. The presence or expression of zinc-positive cells may thus be induced by ingrowth of fibers and terminals from the host brain as transplants placed in the ischemic lesions expressed both zinc-positive neurons and terminals.