Survival and Morphology of Transplanted Astroeytes in Normal and Brain-Damaged Rats

Neurotoxic lesions of nucleus basalis magnocellularis (NBM) in rats cause depletion of acetylcholine (ACh) in neocortex (Ncx) and deficits in passive avoidance (PA) behavior. Such deficits in behavior can be used to evaluate treatments designed to promote functional recovery. Because cultured astrocytes produce, store and release trophic factors known to enhance the rescue of damaged neurons, they were selected for grafting into the damaged NBM. Astrocytes were implanted either directly into the damaged NBM or into the cholinergic cortical projection areas of the NBM. This study evaluates the role of cultured rat primary astrocytes in protecting structures of the central nervous system (CNS) affected by neurotoxic damage of the NBM. Adult male albino rats [Sprague-Dawley (CD), Charles River Labs.] were used in this study. Under sodium pentobarbital (50 mg/kg b.w.) anesthesia, a unilateral injection of ibotenic acid (0.5/zl; 15/zg//zl) was made into the left NBM over a 4 minute duration. Type-l, purified cultured rat primary astrocytes obtained from newborn, CD rat cortex, were prelabeled with fluorescent dye bis-benzimide and transplanted into adult recipient brains. Transplantation of astrocytes into NBM or cortex of NBM damaged animals followed 30 min after injection of ibotenic acid. Location of the transplants and the experimental conditions of the host animals were as follows: 1. Transplantation into NBM of intact animals (n=4); 2. Transplantation into Ncx of intact animals (n=5); 3. Transplantation into NBM of NBM damaged animals (n-22); 4. Transplantation into ipsilateral Ncx of NBM damaged animals (n=4).