Neuroinflammation

Neuroinflammation is the inflammatory response that occurs inside the brain and spinal cord, driven mainly by resident cells rather than by circulating leukocytes. Microglia, the brain's tissue macrophages, and reactive astrocytes shift phenotype after injury or infection and release cytokines such as interleukin-1 beta, interleukin-6 and tumour necrosis factor alpha. Because the blood-brain barrier restricts immune cell traffic, the process differs from peripheral inflammation in cast and timescale.

It is measured indirectly. Translocator protein PET ligands index activated glia but bind a protein whose affinity varies with a common genetic polymorphism, so signal is not simply proportional to inflammation. Fluid markers such as glial fibrillary acidic protein and neurofilament light are now measurable in blood, not only cerebrospinal fluid. Clinical attempts to intervene have been sobering: minocycline, protective in several rodent models, was associated with faster functional decline than placebo in a randomised trial in amyotrophic lateral sclerosis.

The distinction that matters is between acute and sustained activation. A transient glial response clears debris and supports repair; chronic activation sustains excitotoxic and oxidative injury and is a feature of neurodegenerative disease. That makes it a marker of an ongoing process rather than proof that suppressing it will help, and it explains why broadly anti-inflammatory drugs have not translated into disease modification.

The error to watch for is a compound described as anti-neuroinflammatory on the strength of lowered cytokines in a lipopolysaccharide-challenged mouse or a cultured microglial line. That model reports on an acute endotoxin response, not on chronic human neurodegeneration, and the concentrations used in culture are frequently unreachable in brain tissue.