MANF attenuates neuronal apoptosis and promotes behavioral recovery via Akt/MDM‐2/p53 pathway after traumatic spinal cord injury in rats

Abstract

The aim of this study was to investigate the potential effect and mechanism of action of MANF in attenuating neuronal apoptosis following t-SCI. A clip compressive model was used to induce a crush injury of the spinal cord in a total of 230 rats. The Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content, and blood spinal cord barrier (BSCB) permeability were evaluated. The expression levels of MANF and its downstream proteins were examined by western blotting. Immunofluorescence staining of MANF, NeuN, GFAP, Iba-1, cleaved caspase-3, and TUNEL staining were also performed. Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites (2 mm rostral and caudal to the epicenter of the injury) per sample. A cell-based mechanical injury model was also conducted using SH-SY5Y cells. Cell apoptosis and viability were assessed by flow cytometry, an MTT assay, and trypan blue staining. Subcellular structures were observed by transmission electron microscopy. MANF was mainly expressed in neurons. The expression levels of MANF, and its downstream target, p-Akt, were gradually increased and after t-SCI. Treatment with MANF increased Bcl-2 and decreased Bax and CC-3 levels; these effects were reversed on treatment with MK2206. The BBB score, spinal cord water content, and BSCB destruction were also ameliorated by MANF treatment. MANF decreases neuronal apoptosis and improves neurological function through Akt/MDM-2/p53 pathway after t-SCI. Therefore, MANF might be a potential treatment for patients with t-SCI.© 2018 BioFactors, 2018.

Natrium Benzoate Alleviates Neuronal Apoptosis via the DJ-1-Related Anti-oxidative Stress Pathway Involving Akt Phosphorylation in a Rat Model of Traumatic Spinal Cord Injury

“…Apart from neuronal apoptosis, t-SCI also induces edema and BSCB breakdown, which are the major pathological changes and contribute to a poor prognosis (Gao et al, 2018). In the clip compressive model of t-SCI, the compression forces applied to spinal cord can mutilate blood vessels, damage cellular components, and breakdown BSCB (Casella et al, 2006; Dulmovits and Herman, 2012).…”

Euxanthone inhibits traumatic spinal cord injury via anti-oxidative stress and suppression of p38 and PI3K/Akt signaling pathway in a rat model

“…Earlier investigations have suggested that cell necrosis is the predominant landmark of SCI [ 43 , 44 ]. Also, reports claim that resulting necrosis and inflammation of the spinal cord associated neurons after primary mechanical damage are linked with apoptosis [ 43 , 45 ].…”

Increased MANF Expression in the Inferior Temporal Gyrus in Patients With Alzheimer Disease

“…To determine whether MANF is mainly expressed in neurons and to determine its subcellular localization, we performed double immunofluorescence labeling of MANF/neuronal nuclei (NeuN) and MANF/GRP78 as previously described ( Shen et al, 2012 ; Gao et al, 2018 ; Herranen et al, 2020 ), with minor modifications to the protocol. The following antibodies were used: rabbit polyclonal anti-MANF (1:400 dilution); mouse monoclonal anti-NeuN (clone A60, cat.…”