title: Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats.
abstract: Ischemic brain injury in neonates can result in the degeneration of cortical and subcortical areas of brain and is associated with neurologic deficits. One approach to restoring function in conditions of ischemic brain injury is the use of neural transplants to repair damaged connections. This approach has been shown to reestablish neural circuitry and to ameliorate associated motor deficits in models of neonatal sensorimotor cortex damage. In this study, we utilized the Rice et al. rodent model of neonatal ischemic-hypoxic (IH) brain injury to assess whether transplantation of fetal neocortical tissue can promote functional recovery in tests of sensorimotor and locomotor ability throughout development and as adults. We show that animals that received neocortical grafts 3 days following the IH injury performed significantly better as adults on two measures of motor ability, the Rota-Rod treadmill and apomorphine-induced rotations, than did control animals that received sham transplants after the IH injury. Transplants were identifiable in 72% of the animals 10-12 weeks after implantation. Histochemical studies revealed that while the transplanted tissue did not establish normal cortical cytoarchitecture, cells and fibers within the grafts stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), choline acetyl transferase (ChAT), cholecystokinin (CCK), and glial fibrillary acidic protein (GFAP). These results suggest that transplantation of fetal neocortical tissue following IH injury in the neonatal period is associated with amelioration of motor deficits and that the grafted tissue demonstrated a neurochemical phenotype that resembled normal neocortex. This approach warrants continued investigation in light of potential therapeutic uses.
authors.affiliation: Department of Neurosurgery, Graduate Program in Neuroscience, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Jansen
authors.forename: L
authors.initials: L
authors.lastname: Solberg
authors.forename: S
authors.initials: S
authors.lastname: Underhill
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Cozzari
authors.forename: B K
authors.initials: BK
authors.lastname: Hartman
authors.forename: P L
authors.initials: PL
authors.lastname: Faris
authors.forename: W C
authors.initials: WC
authors.lastname: Low
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000633:toxicity; D001925:Brain Damage, Chronic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D016380:Brain Tissue Transplantation / Q000473:pathology; D005311:Fetal Hypoxia / Q000150:complications* / Q000473:pathology; D016332:Fetal Tissue Transplantation / Q000473:pathology; D002534:Hypoxia, Brain / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D009069:Movement Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019579:Neocortex / Q000473:pathology / Q000637:transplantation*; D009410:Nerve Degeneration; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D012678:Sensation Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D001058:Apomorphine