Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity.
In the central nervous system, including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues.
The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells.
However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response.
Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood brain barrier.
The onset of aneurysmal subarachnoid hemorrhage (aSAH) elicits activation of the inflammatory cascade, and ongoing neuroinflammation is suspected to contribute to secondary complications, such as vasospasm and delayed cerebral ischemia.
In a review, of Watson et al. analyze the extent literature regarding the relationship between neuroinflammation and cognitive dysfunction after aSAH. Pro-inflammatory cytokines appear to play a role in maintaining normal cognitive function in adults unaffected by aSAH. However, in the setting of aSAH, elevated cytokine levels may correlate with worse neuropsychological outcomes. This seemingly dichotomous relationship between neuroinflammation and cognition suggests that the action of cytokines varies, depending on their physiologic environment. Experimental therapies which suppress the immune response to aSAH appear to have a beneficial effect on cognitive outcomes. However, further studies are necessary to determine the utility of inflammatory mediators as biomarkers of neurocognitive outcomes, as well as their role in the management of aSAH 1).
Neuroinflammation has been increasingly implicated as a pathological mechanism in dementia and demonstration that it is a key event accelerating cognitive or functional decline would inform novel therapeutic approaches, and may aid diagnosis. Much research has therefore been done to develop technology capable of imaging neuroinflammation in vivo.
The majority of the studies used positron emission tomography (PET) imaging of the TSPO microglial marker and found increased neuroinflammation in at least one neuroanatomical region in dementia patients, most usually Alzheimer's disease, relative to controls, but the published evidence to date does not indicate whether the regional distribution of neuroinflammation differs between dementia types or even whether it is reproducible within a single dementia type between individuals. It is less clear that neuroinflammation is increased relative to controls in mild cognitive impairment than it is for dementia, and therefore it is unclear whether neuroinflammation is part of the pathogenesis in early stages of dementia. Despite its great potential, a review of Stefania et al. demonstrates that imaging of neuroinflammation has not thus far clearly established brain inflammation as an early pathological event. Further studies are required, including those of different dementia subtypes at early stages, and newer, more sensitive, PET imaging probes need to be developed 2).