Propofol post-conditioning protects the blood brain barrier by decreasing matrix metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral outcome in a rat model of focal cerebral ischemia-reperfusion injury

Abstract

Abstract. Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by ischemic stroke, protects the brain from ischemia/reperfusion injury and improves neuronal function. However, whether propofol is able to protect the blood brain barrier (BBB) and the underlying mechanisms have remained to be elucidated. In the present study, a rat model of cerebral ischemia/reperfusion was established, using a thread embolism to achieve middle cerebral artery occlusion. Rats were treated with propofol (propofol post-conditioning) or physiological saline (control) administered by intravenous injection 30 min following reperfusion. Twenty-four hours following reperfusion, neurobehavioral manifestations were assessed. The levels of cephaloedema, damage to the BBB and expression levels of matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun N-terminal kinase (pJNK) were determined in order to evaluate the effects of propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group, the levels of brain water content and Evans blue content, as well as the expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the propofol post-conditioning group. These results indicated that propofol post-conditioning improved the neurobehavioral manifestations and attenuated the BBB damage and cephaloedema induced following cerebral ischemia/reperfusion. This effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the concurrent decrease in JNK phosphorylation.

The impact of general anesthesia, baseline ASPECTS, time to treatment, and IV tPA on intracranial hemorrhage after neurothrombectomy: pooled analysis of the SWIFT PRIME, SWIFT, and STAR trials

“…Although GA did not impact the most severe hemorrhage subtypes (sICH and PH), these findings provide signals about its protective effect against hemorrhage that warrant further exploration. While no definitive explanation regarding the relationship between GA and ICH can be drawn from our data, there are several theoretical possibilities: (1) less patient motion in the setting of GA with more precise intracranial navigation and lower chance of microvascular avulsion; (2) protective effect of anesthetic medications against cerebral ischemic reperfusion injury12–15; (3) reduced pain and agitation with lower chance of blood pressure surges and uncontrolled hypertension, which is an independent risk of HT 16. In addition, hypotension that frequently occurs with GA during thrombectomy may also protect the ischemic tissue against HT after reperfusion.…”

Hyperosmolarity-induced AQP5 upregulation promotes inflammation and cell death via JNK1/2 Activation in human corneal epithelial cells

“…Some of stresses known to induce increases in the JNK1/2 phosphorylation status include, exposure to reactive oxygen species (ROS), mechanical shear stress and a hyperosmolar challenge 13, 44, 45 . In vitro and in vivo results showed that LPS decreases AQP5 expression through the p-JNK/NF-κβ signaling pathway 46, 47 .…”

Relationships between adiponectin and matrix metalloproteinase-9 (MMP-9) serum levels and postoperative cognitive dysfunction in elderly patients after general anesthesia

“…The overexpression of MMP-9 affects the integrity of the vascular basal membrane, thus resulting in severe blood–brain barrier damage and the entry of plasma proteins and a variety of substances and metabolites into the brain, which causes vasogenic edema and the entry of inflammatory cells into brain tissues [7–9]. Reductions in the expression of MMP-9 have been shown to significantly improve cerebral ischemia–reperfusion injuries in rats [10]. However, it is unclear if serum ADP and MMP-9 are involved in the pathophysiological processes underlying POCD.…”