Ion channel blockers and spinal cord injury

Abstract

The activation of a delayed secondary cascade of unsatisfactory cellular and molecular responses after a primary mechanical insult to the spinal cord causes the progressive degeneration of this structure. Disturbance of ionic homeostasis is part of the secondary injury process and plays an integral role in the early stage of spinal cord injury (SCI). The secondary pathology of SCI is complex and involves disturbance of the homeostasis of K(+) , Na(+) , and Ca(2+) . The effect of ion channel blockers on chronic SCI has also been proved. In this Mini-Review, we provide a comprehensive summary of the effects of ion channel blockers on the natural responses after SCI. Combination therapy is based on the roles of ions and disturbance of their homeostasis in SCI. The effects of ion channel blockers suggest that they have potential in the treatment of SCI, although the complexity of their effects shows that further knowledge is needed before they can be applied clinically.

Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art

“…Tetrodotoxin (TTX) is a low-molecular-weight guanidine neurotoxin that acts as a specific blocker of voltage-gated sodium (NaV) channel [17]. TTX has neuroprotective properties by blocking NaV channels, preventing neuronal death by diminishing depolarization, cellular Na + /Ca +2 exchange, and neuronal glutamate release [18].…”

“…The beneficial effects of TTX in preclinical studies include a reduction of white matter loss after SCI [17][18][19], promoting a motor function restoration. The effect of TTX is time-dependent [20].…”

Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats

“…Afterwards, the secondary neurodegenerative events start and worsen the initial injury. Excessive accumulation of intracellular calcium is a common phenomenon after SCI and it is the most critical step in ionic dysregulation that generates axonal injury and eventual apoptosis or necrosis via an increase in cellular enzymes activation, mitochondrial damage, acidosis, and free radicals production [4-9]. …”

Bone marrow stromal cells inhibit caspase-12 expression in rats with spinal cord injury

“…Therefore, it is important to gain an understanding of the pathophysiology underlying SCI in order to develop clinical treatment strategies (1,2). Typically, there are two phases of SCI; the primary injury, in which mechanical impact is afflicted directly on the spine, and the secondary injury, which involves a complex cascade of molecular events, including disturbances in ionic homeostasis (3), local edema, vascular abnormalities, ischemia-reperfusion, glutamate excitotoxicity and inflammatory responses (4–6). Previous studies have indicated that, following SCI, stress responses of the endoplasmic reticulum (ER) drive neurons and oligodendrocytes towards apoptosis (7).…”