Dynamic secondary degeneration in the spinal cord and ventral root after a focal cerebral infarction among hypertensive rats

Abstract

Cerebral infarction can cause secondary damage to nonischemic brain regions. However, whether this phenomenon will appear in central nervous system regions outside the brain remains unclear. Here we investigated pathological changes in the spinal cord and ventral root after ischemic stroke. All rats exhibited apparent neurological deficits post-MCAO, which improved gradually but could still be detected 12-weeks. Neuronal filaments in the corticospinal tract (CST) and neurons in the ventral horn were significantly declined in the contralateral cervical and lumbar enlargement 1-week post-MCAO. These decreases remained stable until 12-weeks, accompanied by progressively increased glial activation in the ventral horn. Axonal degeneration and structural derangement were evident in the contralateral cervical and lumbar ventral root 1-week post-MCAO; these changes spontaneously attenuated over time, but abnormalities could still be observed 12-weeks. The number of neural fibers in the contralateral CST and neurons in the contralateral ventral horn were positively correlated with neurological scores 12-weeks post-MCAO. Additionally, GFAP+cell density in the contralateral CST and ventral horn was negatively correlated with neurological scores. Our results suggest that cerebral infarction can elicit secondary degeneration in the cervical and lumbar spinal cord, as well as the projecting ventral root, which may hamper functional recovery after stroke.

The Involvement of DDAH1 in the Activation of Spinal NOS Signaling in Early Stage of Mechanical Allodynia Induced by Exposure to Ischemic Stress in Mice

“…24) Our previous study showed that activated spinal microglia is observed in BCAO model mice. 9) In general, activated microglia releasing inflammatory cytokines is considered to be involved in the exacerbation of functional recovery after stroke and in the development of chronic pain. 10,25,26) Therefore, it was possible that the upregulation of spinal DDAH1 may be induced by microglial activation, which was observed in BCAO model mice.…”

“…Because, our previous study have shown that increment of spinal HMGB1 signaling induced upregulation of NOS activity on day 3 after BCAO. 9) It has been previously reported that the i.t. administration of L-NAME completely reversed the reduction of paw withdrawal threshold induced by intraperitoneal administration of oxaliplatin.…”

“…It has been recently reported that cerebral infarction could elicit secondary degeneration in non-ischemic areas, such as the spinal cord. [8][9][10] There is evidence that, in mice, nitric oxide synthetase (NOS) is upregulated in the spinal cord after stroke as follows. Generally, NOS is involved in the synthesis of L-citrulline and nitric oxide (NO) from L-arginine, and its activity is affected by various factors, such as ischemic stress or noxious stimuli.…”

“…14,15) Our results also demonstrated that spinal NOS activity increased in the CPSP model in mice. 9) The alternation of spinal NOS signaling may be involved in the exacerbation of ischemic stress damage and/or the development of chronic pain. N (G) ,N (G) -Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a methylated arginine degrading enzyme which is present in various tissues of the central and peripheral regions.…”

Impaired microglia process dynamics post‐stroke are specific to sites of secondary neurodegeneration

“…SND involves the progressive death of neurons that were connected to the site of infarction but not initially damaged by the stroke. SND unfolds over a longer time scale than the infarction process and has recently been implicated as a potential modulator to a number of late phase functional recovery disturbances (Chen, Garcia, Huang, & Constantini, ; Dang et al, ; Fernandez‐Andujar et al, ).…”