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Transplantation of neural stem cells for replacing neurons after neurodegeneration requires that the transplanted stem cells accurately reestablish the lost neural circuits in order to restore function. Retinal ganglion cell axons project to visual centers of the brain forming circuits in precise topographic order. In chick, dorsal retinal neurons project to ventral optic tectum, ventral neurons to dorsal tectum, anterior neurons to posterior tectum and posterior neurons to anterior tectum; forming a continuous point-to-point map of retinal cell position in the tectal projection. We found that when stem cells derived from ventral retina were implanted in dorsal host retina, the stem cells that became ganglion cells projected to dorsal tectum, appropriate for their site of origin in retina but not appropriate for their site of implant in retina. This led us to ask if retinal progenitors exhibit topographic markers of cell position in retina. Indeed, retinal neural progenitors express topographic markers: dorsal stem cells expressed more Ephrin B2 than ventral stem cells and, conversely, ventral stem cells expressed more Pax-2 and Ventroptin than dorsal stem cells. The fact that neural progenitors express topographic markers has pertinent implications in using neural stem cells in cell replacement therapy for replacing projecting neurons that express topographic order, e.g., analogous neurons of the visual, auditory, somatosensory and motor systems., (Published by Elsevier Ltd.)

Using a consistent, reproducible and reliable cortical focal ischemia in rat (permanent unilateral occlusion of the left middle cerebral artery & the ipsilateral common carotid artery [MCAo + CCAo] with a 1 h temporary occlusion of the contralateral CCA), the levels of four major membrane fatty acids (palmitic, C16:0; stearic, C18:0; Oleic, C18:1 and arachidonic, C20:4) were analyzed at 3, 36 and 72 h, and 2 and 4 wk following ischemia to determine the critical point of irreversibility of the cellular plasma membrane disorganization in primary ischemic (Area 1, parietal cortex) and peri-ischemic (Area 2, tempero-occipital cortex) areas. The cortical focal ischemia resulted in time dependent differential loss in four of these major membrane fatty acids. The quantitative differences among primary and peri-ischemic areas reflected the different degree of ischemic injury inflicted to these regions. Acute treatment with ganglioside GM1 protected the further losses of all of these fatty acids and differentially restored their levels in these various injury sites over periods of time. The changes in levels of these membrane fatty acids indicate that the primary ischemic area suffers an irreversible injury and peri-ischemic area suffers reversible injury. After acute treatment (< 2 h) with ganglioside GM1, a partial recovery was observed in primary ischemic area and complete recovery was observed in peri-ischemic areas. These studies support the hypothesis that, ischemia leads to a irreversible plasma membrane disorganization which underlies the eventual cell death, and protection and restoration of these membrane changes by drugs, such as ganglioside GM1 leads to neuroprotection against ischemic injury.

The effects of oxazepam and diazepam (both at 10 mg/kg, i.p.) during continuous treatment for 15 days and following discontinuation after 5 days onwards on cerebral glutamic acid decarboxylase (GAD) and GABA-aminotransferase (GABA-T) have been studied. It has been found that during continuous treatment as well as following discontinuation after 5 days, a significant increase in GAD activity is observed in case of diazepam but not in case of oxazepam. On the other hand, a marked decrease in GABA-T activity is observed during continuous treatment up to 15 days with both diazepam and oxazepam but during discontinuation phase, the decreased GABA-T activity tends to increase and attain normal value much earlier in case of oxazepam than diazepam. This differential effect of oxazepam and diazepam on ?-aminobutyric acid (GABA) metabolism, following discontinuation of treatment, may possibly contribute to the difference in withdrawal effects associated with the two benzodiazepines.