Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury.

Recent studies suggest that the injured adult spinal cord responds to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) with enhanced neuron survival and axon regeneration. Potential neurotrophin sources and cellular localization in spinal cord are largely undefined. We examined glial BDNF localization in normal cord and its temporospatial distribution after injury in vivo. We used dual immunolabeling for BDNF and glial fibrillary acidic protein (GFAP) in astrocytes, adenomatous polyposis coli tumor suppressor protein (APC) for oligodendrocytes or type III CDH receptor (OX42) for microglia/macrophages. In normal cord, small subsets of astrocytes and microglia/macrophages and most oligodendrocytes exhibited BDNF-immunoreactivity. Following injury, the number of BDNF-immunopositive astrocytes and microglia/macrophages increased dramatically at the injury site over time. Most oligodendrocytes contained BDNF 1 day and 1 week following injury, but APC-positive cells were largely absent at the injury site 6 weeks postinjury. Glial BDNF-immunolabeling was also examined 10 and 20 mm from the wound. Ten millimeters from the lesion, astrocyte and microglia/macrophage BDNF-immunolabeling resembled that at the injury at all times examined. Twenty millimeters from injury, BDNF localization in all three glial subtypes resembled controls, regardless of time postlesion. Our findings suggest that in normal adult cord, astrocytes, oligodendrocytes, and microglia/macrophages play roles in local trophin availability and in trophin-mediated injury and healing responses directly within and surrounding the wound site.

Dougherty KD ，Dreyfus CF ，Black IB 《NEUROBIOLOGY OF DISEASE》

Cell proliferation and replacement following contusive spinal cord injury.

Zai LJ ，Wrathall JR 《GLIA》

Targeted retrograde gene delivery of brain-derived neurotrophic factor suppresses apoptosis of neurons and oligodendroglia after spinal cord injury in rats.

Nakajima H ，Uchida K ，Yayama T ，Kobayashi S ，Guerrero AR ，Furukawa S ，Baba H ... -  《-》

Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury.

Spinal cord injury induces a complex cascade of degenerative and remodeling events evolving over time. The possible roles of changed intercellular communication via gap junctions after spinal cord injury (SCI) have remained relatively unexplored. We investigated the temporospatial expression patterns of gap junctional genes and proteins, connexin 43 (Cx43), Cx36, and Cx32, by in situ hybridization and immunohistochemistry in the rat neonatal, adult normal, and adult injured spinal cord. Cx36 was strongly expressed in immature neurons, and levels declined markedly during development, whereas Cx43 and Cx32 persisted throughout adulthood. After a complete transection of the adult spinal cord, the levels of Cx43 mRNA and protein were up-regulated within hours, especially in gray matter rostral to the lesion, reaching over three times normal levels at 4 weeks postinjury. Cx43 immunoreactivity was seen primarily in astrocytes and rarely in microglia. In contrast, Cx36 and Cx32 mRNA and proteins were relatively sparse and unchanged after spinal cord injury along the entire axis of the spinal cord. Cx43 is the most abundant gap junctional protein in the adult CNS and has been shown to form channels between astrocytes as well as between astrocytes and oligodendrocytes. Long-term up-regulation of Cx43 in reactive astrocytes may be one critical component in the rearrangement of the local astroglial network following SCI.

Lee IH ，Lindqvist E ，Kiehn O ，Widenfalk J ，Olson L ... -  《JOURNAL OF COMPARATIVE NEUROLOGY》

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice.

Uchida K ，Nakajima H ，Hirai T ，Yayama T ，Chen K ，Guerrero AR ，Johnson WE ，Baba H ... -  《-》