An Antioxidant and Anti-ER Stress Combo Therapy Decreases Inflammation, Secondary Brain Damage and Promotes Neurological Recovery following Traumatic Brain Injury in Mice

• DOI: 10.1523/jneurosci.0212-22.2022
• Publication Date: 2022-07-28T05:43:00Z
• Authors: Charles K. Davis; Saivenkateshkomal...; Martin Hsu; Kahlilia C. Morri...; Anil K. Chokkalla; Soomin Jeong; Jeongwoo Choi; Shruti Subramanian; Jin Soo Park; Zsuzsanna Fabry; Raghu Vemuganti
• Keywords: Apocynin; Infiltration (HVAC); Brain damage; Pathophysiology

The complex pathophysiology of post-traumatic brain damage might need a polypharmacological strategy with combination drugs that target multiple, synergistic mechanisms. We currently tested apocynin (curtails formation reactive oxygen species), tert-butylhydroquinone (promotes disposal and salubrinal (prevents endoplasmic reticulum stress) following moderate traumatic injury (TBI) induced by controlled cortical impact in adult mice. Adult mice both sexes treated the above tri-combo showed alleviated motor cognitive deficits, attenuated secondary lesion volume, decreased oxidative DNA damage. Concomitantly, treatment regulated post-TBI inflammatory response decreasing infiltration T cells neutrophils activation microglia sexes. Interestingly, sexual dimorphism was seen case TBI-induced microgliosis macrophages tri-combo–treated Moreover, prevented white matter volume loss beneficial effects were long-lasting also aged Thus, present study supports to curtail stress concomitantly as therapeutic improve TBI outcomes. <b>SIGNIFICANCE STATEMENT</b> Of several mechanisms contribute pathophysiology, stress, inflammation play major role. shows potential apocynin, tert-butylhydroquinone, prevent interrelated subjected TBI. include alleviation deficits volume. neuroprotective are linked its ability Importantly, neuroprotection observed be not dependent on sex or age. Our data demonstrate is efficacious after