Axonal sprouting into the denervated spinal cord and synaptic and postsynaptic protein expression in the spinal cord after transplantation of bone marrow stromal cell in stroke rats

Abstract

We investigated whether compensatory reinnervation in the corticospinal tract (CST) and the corticorubral tract (CRT) is enhanced by administration of bone marrow stromal cells (BMSCs) after experimental stroke. Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Phosphate-buffered saline (PBS, control, n=7) or 3 × 10 6 BMSCs in PBS (n=8) were injected into a tail vein at 1 day postischemia. The CST of the left sensorimotor cortices was labeled with DiI 2 days prior to MCAo. Functional recovery was measured. Rats were sacrificed at 28 days after MCAo. The brain and spinal cord were removed and processed for vibratome sections for laser-scanning confocal analysis and paraffin sections for immunohistochemistry. Normal rats (n=4) exhibited a predominantly unilateral pattern of innervation of CST and CRT axons. After stroke, bilateral innervation occurred through axonal sprouting of the uninjured CRT and CST. Administration of BMSCs significantly increased the axonal restructuring on the de-afferented red nucleus and the denervated spinal motoneurons (p<0.05). BMSC treatment also significantly increased synaptic proteins in the denervated motoneurons. These results were highly correlated with improved functional outcome after stroke (r>0.81, p<0.01). We conclude that the transplantation of BMSCs enhance axonal sprouting and rewiring into the denervated spinal cord which may facilitate functional recovery after focal cerebral ischemia.

Suppression of neurocan and enhancement of axonal density in rats after treatment of traumatic brain injury with scaffolds impregnated with bone marrow stromal cells

“…31 This limitation is due to a lack of neurotrophins, but also due to the presence of growth-IMs. 61 These growth-IMs include chondroitin sulfate proteoglycans (for example, neurocan, versican, phosphacan, and brevican), 22 Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp).…”

Triple fluorescence labelling of neuronal, glial and vascular markers revealing pathological alterations in various animal models

“…MCAO is a common model for induction of focal cerebral ischemia (Liu et al, 2007) and this method shows most reproducible and extensive lesions in spontaneously hypertensive rats (Traystman, 2003). Furthermore, the animals present a risk profile including hypertension and hypercholesterolemia which is frequently found in human stroke patients.…”

Preclinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

“…As in stroke studies [23,[37][38][39], the delayed treatments of TBI promoted neurorestorative process in cortical tissue, such as axonal density and reorganization, which fosters improved behavioral function. Without reducing lesion volume, cell-based treatments of stroke in rat also improved functional recovery from the short term (4 weeks) to the long term (1 year) [41,42]. Therefore, the delayed low dose methamphetamine treatment of TBI in rats may improve functional outcome by enhancing biophysical functions of cerebral tissue in the recovery region, although the treatment did not reduce lesion volume and brain atrophy within 6 weeks post TBI.…”

“…Neuronal fiber reorganization after injury may play an important role in fuctional recovery [41,42]. We found that 12 hour post stroke methamphetamine treatment at an infusion dose of 1.0 mg/kg/hr for 24 hours in rats did not reduce infarct volume examined at 7 days post injury, but, did improve neurological scores in rats compared with saline treated controls [18].…”