Amantadine's Neuroprotective Effects in Rabbit Spinal Cord Ischemia/Reperfusion Model

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Spinal cord ischemia-reperfusion injury (SCIRI) is a critical condition leading to significant neurological damage.
• Oxidative stress, inflammation, apoptosis, and tissue necrosis are key pathological mechanisms in SCIRI.
• Existing treatments for SCIRI have limitations, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

• To evaluate the efficacy of amantadine (AMT), a drug with known neuroprotective and anti-inflammatory properties, in an experimental rabbit SCIRI model.
• To investigate the impact of amantadine on oxidative stress markers, tissue necrosis, apoptosis, and neurological recovery following SCIRI.

Main Methods:

• Thirty-two rabbits were allocated into five groups: control, ischemia, vehicle, methylprednisolone (MP), and amantadine (AMT).
• Neurological function was assessed at 24 hours post-injury.
• Spinal cord tissues were collected for biochemical analysis (caspase-3, MDA, MPO, CAT, XO) and histopathological examination.

Main Results:

• SCIRI induced significant increases in caspase-3, MDA, MPO, and XO, and a decrease in CAT levels compared to controls.
• Amantadine (AMT) and methylprednisolone (MP) treatment significantly reduced caspase-3, MDA, MPO, and XO levels, while increasing CAT levels.
• Both AMT and MP groups exhibited improved histopathological scores, increased neuronal survival, and better modified Tarlov scores compared to the ischemia group.

Conclusions:

• Amantadine (AMT) demonstrated significant antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects in the rabbit SCIRI model.
• Biochemical, microscopic, and ultrastructural analyses confirmed the beneficial effects of AMT.
• Amantadine shows potential as a candidate medication for the prophylaxis and treatment of spinal cord ischemia-reperfusion injury.