Anti-inflammatory role of methylprednisolone in the hippocampus prevents depressive-like behavior after spinal cord injury in rats.

Spinal cord injury (SCI) is a debilitating condition that impairs locomotion and frequently leads to psychiatric complications, including anxiety and depression. Neuroinflammation is a central mechanism underlying these behavioral disturbances, as systemic inflammatory signals reach the hippocampus and disrupt neurogenesis. Methylprednisolone (MP), a corticosteroid with potent anti-inflammatory and immunosuppressive properties, is clinically administered in acute SCI to reduce tissue damage. In this study, we examined the effects of acute high-dose MP (30 mg/kg at 30 min and 15 mg/kg at 24 h) on locomotor recovery, anxiety- and depressive-like behaviors, memory, and hippocampal inflammation in female Wistar rats subjected to clip-compression SCI. SCI produced subacute and chronic motor deficits and anxiety- and depressive-like behaviors without impairing exploratory behavior and memory. Acute MP administration prevented depression-like behavior in the sucrose preference test at 8 and 36 postoperative days (POD) and in the social interaction test at 35 POD. However, MP administration was not able to prevent anxiety-like behavior in the light-dark box task at 35 POD and in the elevated plus maze at 32 POD. Moreover, MP treatment reduced hippocampal levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β. These findings demonstrate that MP exerts neuroprotective and anti-inflammatory effects that specifically improve psychosocial outcomes following SCI, underscoring its potential to prevent post-traumatic psychiatric sequelae even in the absence of locomotor recovery.