Acute Intermittent Hypoxia Combined with Motor Training following Cervical Spinal Injury Alters the Glial Fibrillary Acidic Protein (GFAP) expression

Abstract

Spinal cord injury (SCI) is a global neurological disorder that can result in significant functional impairment. The response of astrocytes to SCI, is complex and multifaceted. Astrocytes can play beneficial and detrimental roles in recovery, and the balance between these effects is likely important for functional outcomes. Astrocytes are versatile cells active when the brain and spinal cord sustains injury or damage. Astrocyte activation, or astrogliosis, plays a crucial role in neurological problems, including trauma, infections, stroke, and neurodegeneration. Activated astrocytes demonstrate elevated expression of the intermediate filament GFAP. Recently, acute intermittent hypoxia (AIH, brief exposures to low oxygen (O2) levels alternating with normal O2 levels) presents a fresh approach to non-invasive therapy. AIH has shown tremendous potential to induce spinal plasticity in respiratory and non-respiratory motor neurons and ultimately enhance locomotor function in animals and human subjects with an SCI. The effect of AIH treatment on astrocytes in the spinal cord following SCI, has not been explored. Therefore, this study aims to investigate the impact of AIH treatment and motor training on the expression of GFAP protein in the spinal cord of the SCI rats treated with AIH combined with motor training using immunofluorescence. In this study, we have used the AIH treatment protocol, which has been shown to improve forelimb functional recovery in this lesion model in rats. Specifically, the study assesses GFAP protein expression in the spinal segments of animals with incomplete cervical SCI exposed to AIH treatment + motor training for 1 or 7 days. The protocol of AIH treatment consisted of ten episodes, 5 min 11% O2: 5 min 21% O2 for seven days beginning at four weeks following SCI. AIH treatment and motor training reduced the expression of GFAP in the ventral grey matter at spinal segments C6-7. This effect was evident after seven days of treatment and training but not after one day of therapy and training.

Interestingly, AIH treatment and motor training for one day or seven days did not alter the expression of GFAP protein in the ventral grey matter at L4-5. The current research proposes that the combination of AIH treatment and motor training may mitigate the inflammatory response and decrease the activation of astrocytes in the L4-5 spinal segments of the cord cord after spinal cord injury (SCI). The findings of this study offer valuable perspectives on the therapeutic possibilities of AIH treatment for promoting functional recovery after SCI by modulating astrocyte reactivity. Further investigation is necessary to validate these findings and ascertain the most effective dosage and duration of AIH treatment for maximizing therapeutic benefits in the treatment of SCIs.