EARLY CYTOPATHIC FEATURES IN RAT ISCHEMIA MODEL AND RECONSTRUCTION BYNEURAL GRAFT

Using a silver impregnation (argyrophil III) and immunohistochemistry, acute cytopathic features after cerebral ischemia were investigated. Additionally, functional recovery and interconnection between the host and graft was also explored after neural graft. Animals were embolize d in unilateral middle cerebral artery for 1 h. Argyrophil III method demonstrated ''collapsed'' dark neurons in the striatum, cortex, retic ular thalamus, amygdala, and hypothalamus on ischemic side. These neur ons exhibited characteristic shrunken somata with corkscrew-like dendr ites, suggesting changes in cytoskeletal protein. In the above mention ed areas, the loss of immunoreactivity for mu-calpain proenzyme and mi crotubule-associated protein 2 was also detected. Neural graft into th e ischemic striatum was made 2 weeks after the ischemia paradigm. The grafted striatal cells were prepared from E15 fetuses to make cell sus pension marked by rhodamine-labeled latex microspheres. Methamphetamin e-evoked rotations were detected after ischemia. These motor alteratio ns were reduced gradually but significantly at 8 weeks after the graft . Interconnection between the host and grafted cells was then studied in a brain slice preparation after loading fura-2 AM. About 10% of gra fted cells tested from rats that showed motor amelioration exhibited [ Ca2+](i) increase to the electrical stimulation applied to the neighbo ring host tissue. Data indicate that, in the very early stage after is chemia, cytoskeletal damages, especially on microtubules, started and this would lead to later infarct. The graft survived in the ischemic s triatum having connections with the host, and this might be partly inv olved in the amelioration of motor function. (C) 1996 Academic Press, Inc.