Following acute
spinal cord injury (SCI), excessive recruitment of neutrophils can result in
inflammation, neural tissue loss and exacerbation of neurological outcomes.
Ibrutinib is a
bruton's tyrosine kinase inhibitor in innate immune cells such as the neutrophils that diminishes their activation and influx to the site of injury. The present study evaluated the efficacy of
ibrutinib administration in the acute phase of SCI on neural tissue preservation and locomotor recovery.
Ibrutinib was delivered intravenously at 3.125 mg/kg either immediately, 12 hours after, or both immediately and 12 hours after SCI induction in adult male C57BL/6 mice. Neutrophil influx into the lesion area was evaluated 24 hours following SCI using light microscopy and immunohistochemistry methods. Animals'
body weight changes were recorded, and their functional motor recovery was assessed based on the Basso mouse scale during 28 days
after treatment. Finally, spinal cord lesion volume was estimated by an unbiased stereological method. While animals' weight in the control group started to increase one week after injury, it stayed unchanged in treatment groups. However, the double injection of
ibrutinib led to a significantly lower
body weight compared to the control group at 4 weeks post-injury. Mean neutrophil counts per visual field and the lesion volume were significantly decreased in all
ibrutinib-treated groups. In addition,
ibrutinib significantly improved locomotor functional recovery in all treated groups, especially in immediate and double-injection groups. Neural tissue protection and locomotor functional recovery suggest
ibrutinib treatment as a potent immunotherapeutic intervention for traumatic SCI that warrants clinical testing.