Does inhibition of angiotensin function cause neuroprotection in diffuse traumatic brain injury?

Mohammad Khaksari; Mohammad Amin Rajizadeh; Mohammad Abbas Bejeshk; Zahra Soltani; Sina Motamedi; Fatemeh Moramdi; Masoud Islami; Shahriyar Shafa; Sepehr Khosravi

doi:10.22038/ijbms.2018.26586.6512

June 1, 2018Open Access

Does inhibition of angiotensin function cause neuroprotection in diffuse traumatic brain injury?

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Why the study?

Does candesartan improve neurologic outcomes and reduce brain edema and intracranial pressure in a rat model of diffuse traumatic brain injury?

Structured PICO

Does candesartan improve neurologic outcomes and reduce brain edema and intracranial pressure in a rat model of diffuse traumatic brain injury?

P

Population

Male rats subjected to diffuse traumatic brain injury (TBI)

I

Intervention

Candesartan (0.3 mg/kg) administered intraperitoneally (IP) 30 minutes post-TBI

C

Comparator

Vehicle administered IP 30 minutes post-TBI, sham group, and untreated TBI group

O

Outcome

Brain water content, Evans blue content, intracranial pressure (ICP), neurologic outcome, and oxidant index (malondialdehyde [MDA])surrogate

In a rat model of traumatic brain injury, AT1R blockade with candesartan demonstrated neuroprotective effects by reducing intracranial pressure, brain edema, and blood-brain barrier permeability.

Implication

Candesartan may attenuate edema after experimental TBI; leaves open translation of AT1R blockade to clinical neuroprotection.

Abstract

OBJECTIVES: Neuroprotection is created following the inhibition of angiotensin II type 1 receptor (AT1R). Therefore, the purpose of this research was examining AT1R blockage by candesartan in diffuse traumatic brain injury (TBI). MATERIALS AND METHODS: Male rats were assigned into sham, TBI, vehicle, and candesartan groups. Candesartan (0.3 mg/kg) or vehicle was administered IP, 30 min post-TBI. Brain water and Evans blue contents were determined, 24 and 5 hr after TBI, respectively. Intracranial pressure (ICP) and neurologic outcome were evaluated at -1, 1, 4 and 24 hr after TBI. Oxidant index [malondialdehyde (MDA)] was determined 24 hr after TBI. RESULTS: Brain water and Evans blue contents, and MDA and ICP levels increased in TBI and vehicle groups in comparison with the sham group. Candesartan attenuated the TBI-induced brain water and Evans blue contents, and ICP and MDA enhancement. The neurologic score enhanced following candesartan administration, 24 hr after TBI. CONCLUSION: The blockage of AT1R may be neuroprotective by decreasing ICP associated with the reduction of lipid peroxidation, brain edema, and blood-brain barrier (BBB) permeability, which led to the improvement of neurologic outcome.