J Neurochem. 2026 Sep;170(9):e70553. doi: 10.1111/jnc.70553.
ABSTRACT
The scavenger receptor CD36 is a versatile receptor that regulates various inflammatory processes by interacting with different ligands in concert with other receptors in a context- and cell-type-specific manner. While CD36 is injurious in acute adult stroke, it is beneficial in acute perinatal stroke. This differing acute response may be influenced by the maturation-dependent availability of CD36 receptor partners in the brain, such as Toll-like receptors (TLRs), the developmental state of the blood-brain barrier, and leukocyte subtypes during injury. Here, we further explore CD36-TLR2 interactions in neonatal brain injury by examining whether CD36 similarly affects gene expression and leukocyte trafficking via the blood-CSF barrier/choroid plexus after transient middle cerebral artery occlusion and direct TLR2 stimulation in wild type and CD36 knockout mice. We then examine the consequences of CD36 deficiency for long-term injury outcomes after neonatal stroke. We demonstrate that CD36 deficiency affects long-term behavior performance under physiological conditions and a shift in the role of CD36 from beneficial during acute injury to detrimental in the chronic phase following neonatal stroke. We further show that CD36 contributes to sustained immune responses, as indicated by long-term alterations in microglial phenotypes, and influences long-term functional outcomes. Collectively, these findings underscore the complex time-dependent roles of CD36 and provide insight into the mechanisms by which it modulates ischemic injury in neonatal mice.
PMID:42770491 | DOI:10.1111/jnc.70553