an-vivo-assessment-blood-brain-barrier-disruption-rat-model-ischemic

An <em>In Vivo</em> Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke

Ischemic stroke leads to vasogenic cerebral edema and subsequent primary brain injury, which is mediated through destruction of the blood-brain barrier ...

ardabil university of medical sciences

Central renin angiotensin system has an important role on the cerebral microcirculation and metabolism. Our previous work showed that inhibition of angiotensin converting enzyme (ACE) activity prior to induction of ischemia protected the brain from severe ischemia/reperfusion (I/R) injuries. This study evaluated the impacts of post-ischemic inhibition of ACE, enalapril, on brain infarction in normotensive rats.

Attenuation of focal cerebral ischemic injury following post-ischemic inhibition of angiotensin converting enzyme (ACE) activity in normotensive rat.

1. In the present study, we investigated the effects of postischaemic angiotensin-converting enzyme (ACE) inhibition with enalapril on vasogenic oedema formation and blood-brain barrier (BBB) integrity following transient focal cerebral ischaemia in rats. 2. Cerebral ischaemia was induced by 60 min occlusion of the right middle cerebral artery, followed by 24 h reperfusion. Vehicle and a non-hypotensive dose of enalapril (0.03 mg/kg) were administered at the beginning of the reperfusion period. A neurological deficit score (NDS) was determined for all rats at the end of the reperfusion period. Then, brain oedema formation was investigated using the wet-dry weight method and BBB permeability was evaluated on the basis of extravasation of Evans blue (EB) dye. In addition, oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA) in brain homogenates. 3. Inhibition of ACE by enalapril significantly reduced NDS and decreased brain oedema formation (P < 0.05 for both). Disruption of the BBB following ischaemia resulted in considerable leakage of EB dye into the brain parenchyma of the ipsilateral hemispheres of vehicle-treated rats. Enalapril significantly (P < 0.05) decreased EB extravasation into the lesioned hemisphere. Enalapril also augmented anti-oxidant activity in ischaemic brain tissue by increasing GSH concentrations and significantly (P < 0.05) attenuating the increased MDA levels in response to ischaemia. 4. In conclusion, inhibition of ACE with a non-hypotensive dose of enalapril may protect BBB function and attenuate oedema formation via anti-oxidant actions.

Enalapril attenuates ischaemic brain oedema and protects the blood-brain barrier in rats via an anti-oxidant action.

Angiotensin II (Ang II) has an important role on cerebral microcirculation; however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat.

Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats.

Molecular targeted therapy is an important, novel approach in the treatment of cancer because it interferes with certain molecules involved in carcinogenesis and tumor growth. Examples include monoclonal antibodies, microvesicles, and suicide genes. Several studies have focused on targeted therapies in prostate cancer, which is a serious cause of cancer death in men. We hypothesize that antibody-coated microvesicles can deliver thymidylate kinase, a suicide protein, to prostate cancer cells, potentiating them to death following azidothymidine (AZT) treatment.

Protein Delivery of Thymidylate Kinase Mediated by Tumor-Specific Antibody-Precoated Microvesicles.

This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats.

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

Brain edema aggravates primary brain injury and increases its mortality rate after ischemic stroke. It is believed that normobaric oxygen therapy (NBO) may produce neuroprotective effects against ischemic stroke; however, reports have been controversial, and its effects on vasogenic brain edema as a major complication of brain ischemia have not been clarified. The present study investigates the effects of NBO on cerebral edema and blood - brain barrier integrity using rat model of ischemic stroke. Transient focal cerebral ischemia was induced in adult male Sprague-Dawley rats by left middle cerebral artery occlusion (MCAO) for 90 min followed by 24 h reperfusion. Early NBO supplementation was started 15 min after MCAO and continued for 90 min. The results of the present study show that early oxygen therapy following acute ischemic stroke does not reduce vasogenic brain edema, nor does it protect against oxidative stress-induced BBB destruction. Additionally, cerebral edema formation occurs in conjunction with an increased mortality rate, serious brain injury, and impairment of brain antioxidant power. These findings suggest that further experimental studies should be carried out to clarify the beneficial effects and potential side effects of early oxygen therapy in acute ischemic stroke before its clinical use.

Article	Year
Attenuation of focal cerebral ischemic injury following post-ischemic inhibition of angiotensin converting enzyme (ACE) activity in normotensive rat. Iranian biomedical journal\| PubMed ID: 23183619	2012
Enalapril attenuates ischaemic brain oedema and protects the blood-brain barrier in rats via an anti-oxidant action. Clinical and experimental pharmacology & physiology\| PubMed ID: 24471927	2014
Candesartan attenuates ischemic brain edema and protects the blood-brain barrier integrity from ischemia/reperfusion injury in rats. Iranian biomedical journal\| PubMed ID: 25326022	2014
Protein Delivery of Thymidylate Kinase Mediated by Tumor-Specific Antibody-Precoated Microvesicles. Critical reviews in eukaryotic gene expression\| PubMed ID: 27278881	2016
Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats. Medical principles and practice : international journal of the Kuwait University, Health Science Centre\| PubMed ID: 27606423	2017
Early oxygen therapy does not protect the brain from vasogenic edema following acute ischemic stroke in adult male rats. Scientific reports\| PubMed ID: 28607351	2017

Hamdollah Panahpour

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