Distant microglial and astroglial activation secondary to experimental spinal cord lesion

Abstract

This paper analysed whether glial responses following a spinal cord lesion is restricted to a scar formation close to the wound or they might be also related to widespread paracrine trophic events in the entire cord. Spinal cord hemitransection was performed in adult rats at the thoracic level. Seven days and three months later the spinal cords were removed and submitted to immunohistochemistry of glial fibrillary acidic protein (GFAP) and OX42, markers for astrocytes and microglia, as well as of basic fibroblast growth factor (bFGF), an astroglial neurotrophic factor. Computer assisted image analysis was employed in the quantification of the immunoreactivity changes. At the lesion site an increased number of GFAP positive astrocytes and OX42 positive phagocytic cells characterized a dense scar formation by seven days, which was further augmented after three months. Morphometric analysis of the area and microdensitometric analysis of the intensity of the GFAP and OX42 immunoreactivities showed reactive astrocytes and microglia in the entire spinal cord white and gray matters 7 days and 3 months after surgery. Double immunofluorescence demonstrated increased bFGF immunostaining in reactive astrocytes. The results indicated that glial reaction close to an injury site of the spinal cord is related to wounding and repair events. Although gliosis constitutes a barrier to axonal regeneration, glial activation far from the lesion may contribute to neuronal trophism and plasticity in the lesioned spinal cord favoring neuronal maintenance and fiber outgrowth.

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

“…These results are in line with previous descriptions on the central glial responses after peripheral nerve injury discussed above. It should be mentioned that glial activation does not occur only close to compromised neurons, but also it can be more widespread as recently described for small lesions in the central nervous system 12,[36][37][38] . It is possible that double crush lesion of the sciatic nerve plus local injections performed herein has also triggered some degree of astroglial reaction in the contralateral grey matter of the spinal cord, impairing demonstration of statistical differences antimerically.…”

“…Thus, SC suspension employed in this work was a source of neurotrophic factors. Moreover, a one week spinal cord lesion performed herein in order to obtain the cord extract was suffi cient to trigger a massive astroglial activation with increased level of astroglial neurotrophic factor as well 12 . However, cord extract may also possess a number of toxic substances which are released by degenerated neurons.…”

“…The hypertrophic features of activated astrocytes facilitate environmental recognition, and subsequent deliver of molecules of neurotrophic properties 9 and also immunoregulatory modulators 11 . In fact one of the most important roles of activated astrocytes is their ability to upregulate the synthesis of neurotrophic factor after neuronal injury triggering neuroprotection, wound/repair, neuroregeneration and neuronal plasticity 12 . Glial cell proliferation in the dorsal horn induced either by diseases or physical trauma of peripheral nerves has recently become into attention because of the possibility of the glial involvement in naturopathic pain.…”

“…Glial cell proliferation in the dorsal horn induced either by diseases or physical trauma of peripheral nerves has recently become into attention because of the possibility of the glial involvement in naturopathic pain. Both infl ammation 1,[3][4][5][6][7][8][9][10][11][12][13][14][15] and nerve injury 16 are able to activate glial cells in the dorsal horn of the spinal cord, which have been related to development and maintenance of persistent pain states 15,17 .Like the astroglia, which respond in the central nervous system after central or peripheral axotomy, Schwann cells, a type of glia encountered in the peripheral nervous system, which form myelin sheet of nerve axons, are also capable to become reactive after axotomy of peripheral nerves 8,18 . Activated SC are also able to release neurotrophic factors contributing to protect and to stimulate neuronal regeneration 8 .…”

Comparison between two surgical techniques for prenatal correction of meningomyelocele in sheep

“…If this was caused by the inflammatory reaction produced by dural suture, this inflammatory reaction may have also contributed for the structural disruption of the spinal cord at the lesion level. Accordingly, studies on acute spinal cord lesion models show that the suppression of the inflammatory response may reduce neuronal lesions (28) . The results of the present study showed that all cases submitted to neurosurgical correction presented premature labor, whereas all cases of simplified correction reached gestation term.…”