Berberine improves motor function recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis via AMPK activation in rats with spinal cord injury

Evidences have supported the neuroprotective potential of berberine (BBR) in brain ischemia and injury. This study aimed to investigating whether BBR has neuroprotective effects on SCI and its mechanisms. Adult male Sprague-Dawley rats (220-250 g) were randomly divided into Sham, SCI, SCI + BBR (40 mg/kg/day), and SCI + BBR (40 mg/kg/day) + Compound C groups. The BBB score showed BBR improved functional recovery obviously 7 days later after SCI. Spinal cord tissue samples were harvested three days after SCI. Apoptotic neurons were assessed by TUNEL assay, and the expression levels of p-AMPK, AMPK, CHOP, cleaved caspase-12, Bcl-2, Bax, and cleaved caspase-3 were determined via Western blot. Furthermore, the influence of BBR on p-AMPK, caspase-12 and CHOP expression was determined via immunofluorescence. Neuronal cell apoptosis after SCI was significantly attenuated by BBR (P<0.01). Moreover, Western blot demonstrated that the expressions of cleaved caspase-12, CHOP, Bax, and caspase-3, which were linked to endoplasmic reticulum stress (ERS) associated apoptosis pathways, were significantly increased after SCI and were inhibited by BBR (P<0.01). However, the expressions of p-AMPK and Bcl-2 were significantly decreased after SCI and ameliorated by BBR (P<0.01). Immunofluorescence analysis indicated that BBR increased p-AMPK positive neurons number, reduced caspase-12 and CHOP positive neurons number following SCI (P<0.01). However, the protective effect of BBR on ERS-related protein expression was abolished by Compound C (P>0.05). Thus, BBR attenuates neuronal apoptosis and improves functional recovery in rats with SCI, and these neuroprotective effects may be associated with ERS inhibition and AMPK activation.