Prevalent in today’s clinical world, stroke and cerebral infarction have often resulted in lasting outcomes on cognitive behavior and physiological function in most patients. In order to limit the effects of neurodegenerative disease, it is crucial to understand the mechanism of brain injury to reduce cell death from cerebral inflammation, as well as re-establish neuronal blood flow and cellular function. A pivotal player in the body’s innate immune response to brain injury is the pleiotropic pro-inflammatory cytokine, Tumor Necrosis Factor Alpha (TNF-α). There is still much to learn about the soluble form of the cytokine’s membrane receptor in cerebral conditions such as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Existing evidence supports the selective inhibition of inflammatory cytokines like TNF-α, as well as engineering inhibitors capable of penetrating the Blood-Brain Barrier (BBB) for novel forms of therapy. Understanding this mechanism through systematic literature review and pre-clinical trials may shed light on potential targets for balancing the positive and negative outcomes of cerebral inflammation. With this knowledge, progress can be made towards reducing the long-term anatomical and behavioral consequences associated with these neurodegenerative diseases.