Survival and integration of transplanted postmitotic human neurons following experimental brain injury in immunocompetent rats

Object. Limitations regarding cell homogeneity and survivability do not aff ect neuronlike hNT cells, which are derived from a human teratocarcinoma ce ll line (Ntera2) that differentiates into postmitotic neurons with exposure to retinoic acid. Because NT2N neurons survive longer than 1 year after tr ansplantation into nude mice brains, the authors grafted these cells into t he brains of immunocompetent rats following lateral fluid-percussion brain injury to determine the long-term survivability of NT2N cell grafts in cort ices damaged by traumatic brain injury (TBI) and the therapeutic effect of NT2N neurons on cognitive and motor deficits. Methods. Seventy-two adult male Sprague-Dawley rats. each weighing between 340 and 370 g, were given an anesthetic agent and subjected to lateral flui d percussion brain injury of moderate severity (2.2-2.5 atm in 46 rats) or to surgery without TBI (shamoperation, 26 rats). Twenty-four hours postinju ry, 10(5) NT2N cells (24 injured animals) or 3 mu l of vehicle (22 injured and 14 control animals) was stereotactically implanted into the periinjured or control cerebral cortex. Motor function was assessed at weekly interval s and all animals were killed at 2 or 4 weeks after their posttraumatic lea rning ability was assessed using a Morris water maze paradigm. Viable NT2N grafts were routinely observed to extend human neural cell adhesion molecul e-(MOC-1)immunoreactive processes into the periinjured cortex at 2 and 4 we eks posttransplantation, although no significant improvement in motor or co gnitive function was noted. Inflammation identified around the transplant a t both time points was assessed by immunohistochemical identification of ma crophages (ED-1) and microglia (isolectin B4). Conclusions. Long-term survival and integration of NT2N cells in the periin jured cortex of immunocompetent rats provides the researcher with an import ant cellular system that can be used to study maturation, regulation, and n eurite outgrowth of transplanted neurons following TBI.