Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

Abstract

Embryonic stem (ES) cells have been investigated in many animal models of injury and disease. However, few studies have examined the ability of pre-differentiated ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to compare the effect of murine ES cells that were pre-differentiated into GABAergic neurons or astrocytes on functional recovery following TBI. Neural and astrocyte induction was achieved by co-culturing ES cells on a bone marrow stromal fibroblast (M2-10B4) feeder layer and incubating them with various mitogenic factors. Rats were initially prepared with a unilateral controlled cortical contusion injury of the sensorimotor cortex or sham procedure. Rats were transplanted 7 days following injury with ∼100K GABAergic neurons, astrocytes, fibroblasts, or media. Animals were assessed on a battery of sensorimotor tasks following transplantation. The stromal fibroblast cells (M2-10B4), as a control cell line, did not differ significantly from media infusions. Transplantation of GABAergic neurons facilitated complete and total recovery on the vibrissae-forelimb placing test as opposed to all other groups, which failed to show any recovery. It was also found that GABAergic neurons reduced the magnitude of the initial impairment on the limb use test. Histological analysis revealed infiltration of host brain with transplanted neurons and astrocytes. The results of the present study suggest that transplantation of pre-differentiated GABAergic neurons significantly induces recovery of sensorimotor function; whereas, astrocytes do not.

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

“…These deficits and forelimb asymmetries did not fully recover over time. The deficits were similar to those previously reported after CCI of the caudal forelimb area of the SMC (Becerra, 2007;Hoane et al, 2007;Nishibe et al, 2010). The severity and extent of the deficits and asymmetrical forelimb use were also similar to those found using the same measures following electrolytic (Kozlowski et al, 1996) or focal ischemic lesions of the FL-SMC (Hsu and Jones, 2006), both of which result in significant post-lesion neuronal growth responses.…”

A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury

“…42,45 Rats were pre-tested for baseline levels on the two days prior to surgery. On each test day, the rats were placed in an empty fish tank (50 cm · 25 cm · 30 cm) and allowed to explore for 120 sec.…”

Stem cells in neurology - current perspectives

“…This is probably influenced by changes in the time of transplantation and the number of transplanted cells 40 . In another study, the transplantation of ESCs pre-differentiated into neuronal and glial precursors resulted in great sensory and motor improvements, but no cognitive improvement 41 , whereas in a similar study with GABAergic neuron transplantation, a greater sensorimotor recovery was observed, which was not seen when astrocytes were transplanted 42 . In yet another study, Gao et al 43 showed that human fetal NSCs pre-differentiated into neurons and then implanted into the hippocampus of TBI animals, were able to differentiate into neurons 1-day after injury, and the animals showed cognitive improvement.…”