A quantitative analysis of the glial cell reaction in primary sensory termination areas following sciatic nerve injury and treatment with nerve growth factor in the adult rat

Abstract

The time course of the astroglial cell reaction in the nucleus gracilis and the spinal cord dorsal horn was examined following sciatic nerve transection in the adult rat with qualitative and quantitative analysis of glial fibrillary acidic protein immunoreactivity and in situ hybridization for its mRNA. In addition, the potential effect of exogenous nerve growth factor (NGF) was examined on the astroglial and microglial cells in the spinal cord dorsal horn at certain time points following sciatic nerve transection. An increase in glial fibrillary acidic protein immunoreactivity as well as mRNA labelling was observed from 1 day after lesioning, with a peak at about 1 week and 2 days after lesioning, respectively, followed by a decline. However, NGF application during 1, 2 and 4 weeks following nerve transection did not result in any significantly reduced astroglial or microglial activity. Our results show that the astroglial cell response in the nucleus gracilis and the spinal cord dorsal horn is rapid in comparison with previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration), that the astroglial cell reaction develops concomitantly with the microglial cell reaction previously described and that the "signal" from the axotomized neurons which induces these reactions can not be prevented by exogenous NGF applied to the peripheral nerve.

Inhibition of Microglial Activation Attenuates the Development but Not Existing Hypersensitivity in a Rat Model of Neuropathy

“…A. DeLeo, manuscript submitted for publication). Similar observations were reported after injury to spinal cord or peripheral nerves (Svensson et al, 1993;Kreutzberg, 1996;Eriksson et al, 1997;Popovich et al, 1997;Gilmore and Kane, 1998), where microglia but not astrocytes proliferate, become hypertrophic, and express several marker molecules and mediators that in turn activate astrocytes. This suggests preemptive minocycline treatment induced-inhibition of hyperalgesia/allodynia and astrogliosis is the consequence of early microglial activation inhibition.…”

“…Reactive astrocytes maintain the state of synaptic differentiation initially associated with the microglial response. After nerve injury, the process of hypertrophic astrocytes takes over the perineuronal position and replaces the microglia (Kreutzberg, 1996;Eriksson et al, 1997;Popovich et al, 1997). Postoperative administration of inhibitors or modulators of astrocytes attenuate chronic pain states, induced by nerve injury or inflammogens (Meller et al, 1994;Watkins et al, 1997;Sweitzer et al, 2001;.…”

Metastasis-associated Mts1 (S100A4) protein is selectively expressed in white matter astrocytes and is up-regulated after peripheral nerve or dorsal root injury

“…Injury to the peripheral branches, e.g., by section of the sciatic nerve, induces degenerative as well as growth-associated changes (transganglionic changes) in the central terminals and axons of the injured neurons (Woolf et al, 1990(Woolf et al, , 1995Aldskogius et al, 1992). Concomitantly, microglial cells proliferate (Gehrmann et al, 1991;Eriksson et al, 1993;Persson et al, 1995) and express various inflammatory mediators (Liu et al, 1995), while astrocytes up-regulate the expression of their major intermediate filament, glial fibrillary acidic protein (GFAP; Gilmore et al, 1990), and GFAP mRNA (Eriksson et al, 1997) but do not proliferate (Liu and Kozlova, 1999). Injury to the central primary sensory process by section of the dorsal root results in complete disintegration (Wallerian degeneration) of the segment of the axon no longer in continuity with the parent cell body.…”

Glial cell responses, complement, and clusterin in the central nervous system following dorsal root transection

“…As a result, there is a marked increase locally in the number of these cells (Cova and Aldskogius, 1986;Cova et al, 1988), a reaction peaking about 1 to 2 weeks postinjury . Concomitantly, astrocytes undergo hypertrophy, as evidenced by the marked increase in immunoreactivity for the major astroglial cell intermediate filament protein, glial fibrillary acidic protein, GFAP (Cheng et al, 1994;Eriksson et al, 1997;Garrison et al, 1991;Gilmore et al, 1990;Hajos et al, 1990;Murray et al, 1990;, and its mRNA (Eriksson et al, 1997). The microglial cells responding to peripheral nerve injury express several complement factors, indicating that the complement cascade is activated Svensson and Aldskogius, 1992a;Svensson et al, 1995).…”