Astrocytes and Microglia-Mediated Immune Response in Maladaptive Plasticity is Differently Modulated by NGF in the Ventral Horn of the Spinal Cord Following Peripheral Nerve Injury

Abstract

Reactive astrocytes and activated microglia are the key players in several pathophysiologic modifications of the central nervous system. We used the spared nerve injury (SNI) of the sciatic nerve to induce glial maladaptive response in the ventral horn of lumbar spinal cord and examine its role in the remodeling of the tripartite synapse plasticity. Imaging the ventral horn revealed that SNI was associated with both an early microglial and astrocytic activation, assessed, respectively, by analysis of Iba1 and GFAP expression. Microglia, in particular, localized peculiarly surrounding the motor neurons somata. Perineuronal astrocytes, which play a key role in maintaining the homeostasis of neuronal circuitry, underwent a substantial phenotypic change following peripheral axotomy, producing reactive gliosis. The gliosis was associated with the reduction of glial aminoacid transporters (GLT1 and GlyT1) and increase of neuronal glutamate transporter EAAC1. Although the expression of GABAergic neuronal marker GAD65/67 showed no change, glutamate increase, as demonstrated by HPLC analysis, shifted the excitatory/inhibitory balance as showed by the net increase of the glutamate/GABA ratio. Moreover, endogenous NGF levels were altered in SNI animals and not restored by the intrathecal NGF administration. This treatment reverted phenotypic changes associated with reactive astrocytosis, but failed to modify microglia activation. These findings on one hand confirm the correlation between gliopathy and maladaptive plasticity of the spinal synaptic circuitry, on the other hand add new data concerning the complex peculiar behavior of different glial cells in neuronal degenerative processes, defining a special role of microglia in sustaining the inflammatory response.

Powerful solution for experimental cerebral malaria treatment: artesunate and tetramethylpyrazine

“…Activation of astrocytes and microglia acts as a crucial player in several pathophysiological changes in the central nervous system (CNS) [25]. Glial fibrillary acidic protein (GFAP) is a key protein expressed in astrocytes and is significantly up-regulated when nerves are damaged [26].…”

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

“…It is known that microglia and astrocytes play a special role in sustaining the immune response [50], so we evaluated the effect of 18B12 on microglial and astrocytic markers. Microglial Iba1 and astrocytic GFAP expression are usually used as markers of glial cells, though their use as markers of cellular activation has been increasingly questioned.…”

Neurons, Glia, Extracellular Matrix and Neurovascular Unit: A Systems Biology Approach to the Complexity of Synaptic Plasticity in Health and Disease

“…Microglia can rapidly sense differences and homeostatic perturbations by scanning other cells (astrocytes and neurons) and the brain ECM ( Figure 1) [108], and surveying the environment for pathogens and autologous debris (phagocytic function) ( Figure 2) as the first cellular line in the innate immune response [14,[109][110][111]. In the last scenario, microglia can mediate the loosening of BBB and the secondary immune reaction [112].…”