Multiple pathomechanisms of cerebral ischemia reperfusion (I/R) injuries can be ameliorated by certain high-potential pharmaceutical substances. In the present study, we investigated the acute effect of p-hydroxycinnamic (pHCA) acid against cerebral I/R injury in mice. Thirty male ICR mice were divided into Sham, Control-I/R, and pHCA-I/R groups. The pHCA 100 mg/kg and the vehicle were given 30 min before I/R induction. Thirty-minute bilateral common carotid artery occlusion followed by 45-min reperfusion was performed on the Control-I/R and pHCA-I/R groups. Brains were collected for biochemical analysis, infarction and histological study of the cerebral cortex and corpus callosum (CC). The results showed that I/R induction significantly induced biochemical changes (p<0.05) along with the increase of brain infarction (p<0.05), percentage of degeneration in cerebral cortex (p<0.05) and decrease of CC white matter density (p<0.05). Pretreatment with pHCA significantly reduced MDA (p<0.05), brain infarction (p<0.05), cerebral cortex neuronal degeneration (p<0.05) and prevented the reduction of white matter density in the CC (p<0.05). The present study concluded that pretreatment with pHCA helps prevent cerebral I/R injury by amelioration of lipid peroxidation, white matter damage and neuronal degeneration. ABSTRAK Pelbagai patologi mekanisme kecederaan serebrum iskemia-reperfusi (I/R) boleh diperbaikkan oleh beberapa bahan farmaseutik berpotensi tinggi. Dalam penyelidikan ini, kami mengkaji kesan akut p-hidroksisinamik (pHCA) terhadap kecederaan I/R serebrum pada tikus. Tiga puluh tikus ICR jantan dibahagikan kepada Sham, kawalan-I/R, dan kumpulan pHCA-I/R. PHCA 100 mg/kg dan pembawa diberikan 30 min sebelum induksi I/R. Oklusi arteri karotid selama 12 min diikuti oleh reperfusi 45 min dilakukan pada kumpulan Kawalan-I/R dan pHCA-I/R. Tisu otak dikumpulkan untuk analisis biokimia, infarksi dan kajian histologi korteks serebrum dan korpus kalosum (CC). Keputusan menunjukkan bahawa induksi I/R menunjukkan perubahan biokimia yang ketara (p<0.05) dengan peningkatan infarksi otak (p<0.05), peratusan degenerasi dalam korteks serebrum (p<0.05). Pra-rawatan dengan pHCA mengurangkan MDA (p<0.05), infarksi otak (p<0.05), degenerasi neuron korteks serebrum (p<0.05) dan menghalang pengurangan kepadatan bahan putih otak di CC (p<0.05). Kajian ini menyimpulkan bahawa prarawatan dengan pHCA membantu mencegah kecederaan otak I/R dengan memperbaik peroksidasi lipid, kerosakan bahan putih otak dan degenerasi neuron. Kata kunci: Asid p-hidroksisinamik; bahan putih otak; infarksi; iskemia otak; tekanan oksidatif