Hydrogen gas post‑conditioning alleviates cognitive dysfunction and anxiety‑like behavior in a rat model of subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) results in high rates of mortality and lasting disability. Hydrogen gas (H 2 ) is an antioxidant with demonstrated neuroprotective efficacy. The present study examined the therapeutic efficacy of H 2 inhalation on early brain injury following experimental SAH in rats and the potential underlying molecular mechanisms. The rats were randomly separated into three groups (n=36 per group): Sham, SAH and SAH + H 2 . Endovascular perforation of the right internal carotid artery was used to establish SAH. After perforation, rats in the SAH + H 2 group inhaled 2.9% H 2 with regular oxygen for 2 h. Then, 24 h post-SAH, TUNEL staining was used to detect apoptotic neurons, and both immunostaining and western blotting were conducted to examine changes in p38 MAPK activity and the expression levels of apoptotic regulators (Bcl-2, Bax and cleaved caspase-3) in the ventromedial prefrontal cortex. Then, 30 day post-SAH, Nissl staining was performed to detect neuronal injury, brain MRI was conducted to detect gross changes in brain structure and metabolism, the open field test was used to assess anxiety and the novel object recognition test was performed to assess memory. H 2 inhalation following experimental SAH stabilized brain metabolites, improved recognition memory and reduced anxiety-like behavior, the neuronal apoptosis rate, phosphorylated p38 MAPK expression, cleaved caspase-3 expression and the Bax/Bcl-2 ratio. Collectively, the present results suggested that H 2 inhalation can alleviate SAH-induced cognitive impairment, behavioral abnormalities and neuronal apoptosis in rats, possibly via inhibition of the p38 MAPK signal pathway.

Hydrogen-Rich Water as a Novel Therapeutic Strategy for the Affective Disorders Linked with Chronic Neuropathic Pain in Mice

“…Concerning the emotional disorders, some studies have shown the promising use of H 2 for treating the depressive-like behaviors provoked by mild chronic unpredictable stress [ 29 ] and the anxiety-like behaviors associated with morphine-withdrawal [ 34 ] or with a subarachnoid hemorrhage in rodents [ 35 ]. Despite that, the effects of H 2 on the emotional disorders accompanying neuropathic pain have not been studied.…”

Defining the Penumbra in a Preclinical Model of Subarachnoid Hemorrhage

“…This is also seen in the clinical literature, in which patients tend to have worsening depression in the initial 12 months following SAH [54]. In preclinical models of SAH, damages to the ventromedial prefrontal cortex, perirhinal cortex, and hypothalamus were associated with the development of anxiety [44,55]. While no studies have directly investigated the anatomic correlates of post-SAH depression, patients with SAH have shown altered functional connectivity in the cingulate cortex, which is also seen in major depressive disorder [56,57].…”

Neurobehavioral Impairments Predict Specific Cerebral Damage in Rat Model of Subarachnoid Hemorrhage

“…The percentage of open arm entry for the EM demonstrated a moderate (> 70%) correlation with and accuracy for predicting damage to the amygdala. While anxiety-like behavior has been frequently reported in experimental models of SAH, no preclinical studies have directly linked SAH-related anxiety to cellular damage in the amygdala [51][52][53].…”