THE ASSESSMENT OF T2 MAP HETEROGENEITY WITHIN THE ISCHAEMIC AREA IDENTIFIES A NOVEL CEREBROPROTECTIVE ROLE OF SUBEROYLANILIDE HYDROXAMIC ACID FOLLOWING TMCAO

Stroke is a medical condition considered the second leading cause of mortality and the third cause of disability in adults worldwide. The main objective of many therapeutic strategies is to reduce infarct volume. However, treatment efficacy is often assessed solely based on regions of interest (ROIs) that delimit the infarcted area. These ROIs are identified using classical staining techniques (e.g., 2,3,5-triphenyltetrazolium chloride, cresyl violet) or conventional magnetic resonance imaging. This quantification approach, however, overlooks the intrinsic heterogeneity within the ischaemic region, which is particularly relevant in the penumbra, where some neurons preserve enough metabolic activity to survive. In the present study, we demonstrate that analysis of T2 maps from the ischaemic area provides a more detailed characterization of damage severity following transient middle cerebral artery occlusion (90 min, tMCAO), and how an epigenetic treatment (suberoylanilide hydroxamic acid) can modulate this damage. ROIs were manually delineated, and T2 pixel intensity values were classified into three categories: mild (<70 ms), moderate (70–90 ms), and severe (>90 ms) tissue damage. Treatment increased the proportion of mildly and moderately damaged tissue while reducing the volume of severely affected regions, both in acute and long-term stages. In summary, evaluating the intrinsic heterogeneity within the injured region may reveal therapeutic effects that could otherwise be overlooked when efficacy is assessed solely by changes in overall ROI size. This novel methodology has the potential to improve preclinical stroke studies by better capturing the spatial and biological complexity of ischaemic brain injury and recovery.