Spinal Cord Injury Impairs Neurogenesis and Induces Glial Reactivity in the Hippocampus

Abstract

The incorporation of newborn neurons with increased synaptic remodeling and activity-dependent plasticity in the dentate gyrus enhances hippocampal-dependent learning performances. Astrocytes and microglial cells are components of the neurogenic niche and regulate neurogenesis under normal and neurophatological conditions leading to functional consequences for learning and memory. Although cognitive impairments were reported in patients after spinal cord injury (SCI), only few studies have considered remote changes in brain structures which are not related with sensory and motor cortex. Thus, we examined neurogenesis and glial reactivity by stereological assessment in dentate gyrus sub-regions after three different intensities of thoracic spinal cord compression in rats. Sixty days after injury we observed a decrease in the Basso-Bresnahan-Beattie locomotor scale scores, rotarod performance and volume of spare tissue that correlated with the severity of the compression. Regarding the hippocampus, we observed that neurogenesis and hilar neurons were reduced after severe SCI, while only neurogenesis decreased in the moderately injured group. In addition, severe SCI induced reactive microglia and astrogliosis in all dentate gyrus sub-regions. Furthermore, the density of reactive microglia increased in the hilus whereas astrogliosis developed in the molecular layer after moderate SCI. No changes were observed in the mildly injured rats. These results suggest glial response and neurogenesis are associated with injury intensity. Interestingly, hippocampal neurogenesis is more sensitive to SCI than astrocytes or microglia reaction, as moderate injury impairs the generation of new neurons without changing glial response in the subgranular zone.

Dementia, Depression, and Associated Brain Inflammatory Mechanisms after Spinal Cord Injury

“…Moreover, flow cytometry analysis demonstrated that moderate/severe SCI in C57BL/6 male mice caused significantly increased levels of proinflammatory cytokine IL6 in the brain ( Figure 2 ). These data complemented microscopy findings showing chronic microglial activation in brain after SCI [ 38 , 39 , 40 , 73 , 74 ]. Glial activation was confirmed in the sub-granular zone and molecular layer of the DG in the hippocampus in a severity-dependent manner; such activation was only found in moderate and severe SCI, but not mild [ 73 ].…”

Evidence for neurogenesis in the medial cortex of the leopard gecko, Eublepharis macularius

“…More specifically, our findings revealed that there is no significant change in proliferation, evidenced by BrdU uptake, between leopard geckos within intact (original) tails and those induced to self-detach their tails. In contrast, among mammals the hippocampal formation is particularly sensitive to spinal cord injuries 36 , 69 . For example, in rats a partial hemisection of the cervical spinal cord results in a significant reduction in the number of BrdU+ cells within 7-days following injury 36 .…”

Delayed Influence of Spinal Cord Injury on the Amino Acids of NO• Metabolism in Rat Cerebral Cortex Is Attenuated by Thiamine

“…Such effects may underlie a well-known increase in frequency of the brain-affecting neurodegenerative diseases after SCI. Indeed, widespread neuroinflammation and microglia activation are landmarks of neurodegeneration in the brain ( 16 ), and several studies have already shown that SCI promotes these processes, also disturbing neurogenesis ( 17 – 19 ). Nevertheless, molecular mechanisms of delayed alterations outside the area of injury have been poorly explored.…”