The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model

Kobeissy, Firas H. and Mallah, Khalil and Zibara, Kazem and Dakroub, Fatima and Dalloul, Zeinab and Nasser, Mohammad and Nasrallah, Leila and Mallah, Zahraa and El-Achkar, Ghewa A and Ramadan, Naify and Mohamed, Wael Mohamed Yousef and Mondello, Stefania and Hamade, Eva and Habib, Aida (2022) The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model. Neurochemistry International, 154. ISSN 01970186

	PDF - Accepted Version Restricted to Registered users only Download (116kB) | Request a copy
	PDF - Accepted Version Restricted to Registered users only Download (181kB) | Request a copy
	PDF (SCOPUS) - Supplemental Material Restricted to Registered users only Download (751kB) | Request a copy
	PDF - Published Version Restricted to Registered users only Download (217kB) | Request a copy

Abstract

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Aspirin (ASA) and clopidogrel (CLOP) are antiplatelet agents that inhibit platelet aggregation. They are implicated in worsening the intracerebral haemorrhage (ICH) risk post-TBI. However, antiplatelet drugs may also exert a neuroprotective effect post-injury. We determined the impact of aspirin and clopidogrel treatment, alone or in combination, on ICH and brain damage in an experimental rat TBI model. We assessed changes in platelet aggregation and measured serum thromboxane by enzyme immune assay. We also explored a panel of brain damage and apoptosis biomarkers by immunoblotting. Rats were treated with aspirin and/or clopidogrel for 48 h prior to TBI and sacrificed 48 h post-injury. In rats treated with antiplatelet agents prior to TBI, platelet aggregation was completely inhibited, and serum thromboxane was significantly decreased, compared to the TBI group without treatment. TBI increases UCHL-1 and GFAP, but decreases hexokinase expression compared to the non-injured controls. All groups treated with antiplatelet drugs prior to TBI had decreased UCH-L1 and GFAP serum levels compared to the TBI untreated group. Furthermore, the ASA and CLOP single treatments increased the hexokinase serum levels. We confirmed that αII-spectrin cleavage increased post-TBI, with the highest cleavage detected in CLOP-treated rats. Aspirin and/or clopidogrel treatment prior to TBI is a double-edged sword that exerts a dual effect post-injury. On one hand, ASA and CLOP single treatments increase the post-TBI ICH risk, with a further detrimental effect from the ASA + CLOP treatment. On the other hand, ASA and/or CLOP treatments are neuroprotective and result in a favourable profile of TBI injury markers. The ICH risk and the neuroprotection benefits from antiplatelet therapy should be weighed against each other to ameliorate the management of TBI patients.

Item Type:	Article (Journal)
Additional Information:	7497/96669
Uncontrolled Keywords:	Aspirin; Clopidogrel; Controlled cortical impact; Intracerebral haemorrhage; Neuroprotection; Traumatic brain injury.
Subjects:	R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine Kulliyyah of Medicine > Department of Basic Medical
Depositing User:	Dr Wael Mohamed
Date Deposited:	09 Feb 2022 16:23
Last Modified:	23 Feb 2022 09:47
URI:	http://irep.iium.edu.my/id/eprint/96669

Actions (login required)

View Item