Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis.

Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.

Persistent isoflurane-induced hypotension causes hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is likely to occur in elderly people, who often suffer from cerebral hypoperfusion and white matter lesions even in the absence of cerebral infarctions. METHODS: Thirty-two adult male rats were randomly assigned to one of four groups: the cerebral normoperfusion + normotension group (n = 8), cerebral normoperfusion + hypotension group (n = 8), chronic cerebral hypoperfusion (CCH) + normotension group (n = 8), and CCH + hypotension group (n = 8). A rat model of CCH was developed via the permanent ligation of the bilateral common carotid arteries, but ligation was avoided in the cerebral normoperfusion groups. Two weeks later, the rats were intubated and mechanically ventilated under isoflurane anesthesia, and their mean arterial blood pressure was maintained over 80 mmHg (normotension) or below 60 mmHg (hypotension) for 2 h. After preparing brain slices, histological cresyl violet staining, ionized calcium binding adaptor molecule 1, a marker of microglial activation, or ß amyloid precursor protein, a marker of axonal damage, were performed. RESULTS AND CONCLUSION: CCH per se caused microglial activation and axonal damage, which was not accentuated by hypotension. CCH alone did not cause neuronal damage, but CCH combined with hypotension caused significant neuronal damage in the hippocampal CA1 region. These results suggest that persistent hypotension during general anesthesia might cause neuronal damage in patients with CCH, such as elderly people, and contribute to prevention against POCD.

Dexmedetomidine Inhibits Hippocampal Neuronal Damage Caused by Persistent Isoflurane-Induced Hypotension in Rat Model of Chronic Cerebral Hypoperfusion.

Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 µg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.

Wistar Rats Hippocampal Neurons Response to Blood Low-Density Polyethylene Microplastics: A Pathway Analysis of SOD, CAT, MDA, 8-OHdG Expression in Hippocampal Neurons and Blood Serum Aß42 Levels.

Purpose: Low-density polyethylene microplastics are ingested into the bloodstream and distributed to all the organ tissue, including the hippocampus, causing toxic effects. This research aimed to elucidate the responses of hippocampal neurons to microplastic in the blood based on the expressions of superoxide dismutase (SOD), catalase (CAT) enzymes, malondialdehyde (MDA), 8-oxo-7,8-dihydro-2-deoxyguanosine (8-OHdG) in hippocampal neurons, and blood serum amyloid beta 1-42 (Aß42) levels using SMART PLS pathway analysis. Methods: This was a pure experimental research on Wistar rats with a post-test control group design. Five experimental groups (X1, X2, X3, X4, X5) were given 0.0375 mg, 0.075 mg, 0.15 mg, 0.3 mg, and 0.6 mg of low-density polyethylene microplastics mixed in 2cc distilled water, respectively. Furthermore, except for control (C), the groups received microplastics an oral probe for 90 days. Results: The molecular response of hippocampal neurons of Wistar rats to microplastics in the blood significantly decreased SOD enzyme expression, while CAT enzyme was unaffected. It considerably increased neuronal membrane damage (expression of MDA), increased considerably neuronal deoxyribonucleic acid damage (expression of 8-OHdG), and decreased blood serum Aß42 levels (pathway analysis, all t-value >1.96). Conclusion: The pathway analysis showed that hippocampal neurons were significantly affected by microplastic particles in the blood.