<p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem; color: rgb(33, 33, 33); font-family: BlinkMacSystemFont, -apple-system, &quot;Segoe UI&quot;, Roboto, Oxygen, Ubuntu, Cantarell, &quot;Fira Sans&quot;, &quot;Droid Sans&quot;, &quot;Helvetica Neue&quot;, sans-serif; font-size: 16px;"><strong class="sub-title" style="box-sizing: inherit;">Purpose:&nbsp;</strong>The ischemia-reperfusion (I/R) injury seen in the heart can cause severe damage to essential organs such as the brain. Cannabidiol (CBD) obtained from Cannabis sativa is used today to treat various diseases. This study aimed to demonstrate CBD's neuroprotective and therapeutic properties in rats with brain damage caused by I/R in the heart.</p><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem; color: rgb(33, 33, 33); font-family: BlinkMacSystemFont, -apple-system, &quot;Segoe UI&quot;, Roboto, Oxygen, Ubuntu, Cantarell, &quot;Fira Sans&quot;, &quot;Droid Sans&quot;, &quot;Helvetica Neue&quot;, sans-serif; font-size: 16px;"><strong class="sub-title" style="box-sizing: inherit;">Materials:&nbsp;</strong>Rats were divided into four groups; sham, I/R, I/R + Prophylactic CBD, and I/R + Therapeutic CBD. End of the experiment, brain tissues were collected for biochemical, histopathological, and genetic examinations.</p><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem; color: rgb(33, 33, 33); font-family: BlinkMacSystemFont, -apple-system, &quot;Segoe UI&quot;, Roboto, Oxygen, Ubuntu, Cantarell, &quot;Fira Sans&quot;, &quot;Droid Sans&quot;, &quot;Helvetica Neue&quot;, sans-serif; font-size: 16px;"><strong class="sub-title" style="box-sizing: inherit;">Results:&nbsp;</strong>I/R damage increased the number of degenerative neurons, caspase-3 and TNF-α immunoexpression, total oxidant status levels, and oxidative stress index. Both prophylactic and therapeutic CBD administration reduced these increased values. In addition, the relative fold changes of AMPK, PGC-1α, SIRT1, and Bcl 2 decreased in the I/R group, and the relative fold change of Bax increased, which are indicators of ER stress and apoptosis. Both administrations of CBD reversed these genes' relative fold changes.</p><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem; color: rgb(33, 33, 33); font-family: BlinkMacSystemFont, -apple-system, &quot;Segoe UI&quot;, Roboto, Oxygen, Ubuntu, Cantarell, &quot;Fira Sans&quot;, &quot;Droid Sans&quot;, &quot;Helvetica Neue&quot;, sans-serif; font-size: 16px;"><strong class="sub-title" style="box-sizing: inherit;">Conclusion:&nbsp;</strong>CBD can be protective against brain injury caused by cardiac I/R damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.</p>