How Neuroinflammation Occurs through the Central Nervous System
Neuroinflammation is an inflammatory response that occurs when the central nervous system’s (CNS) homeostasis is disrupted. The trigger may be one of a number of inflammatory issues, including those resulting from neurodegenerative disease, toxin exposure, injury, or infection. It’s a pathology commonly found in a number of chronic ailments of the brain, including Alzheimer’s, Parkinson’s, and Huntington disease. It’s also associated with schizophrenia, autism, and depression, though the exact mechanisms are not well understood.
Running between the brain and the spine, the central nervous system (CNS) is a conduit for immune modulated responses, which help keep harmful infections, viruses, and diseases at bay. In understanding the exact dynamics of neuroinflammation it’s important to understand the relationship between microglia and astrocytes. Both are cell types, with microglia an immune cell that resides throughout the CNS. Tasked with brain development and immune surveillance, microglia help ensure tissue homeostasis, as well as a well-regulated immune system.
A primary task of astrocytes is controlling blood flow and the levels at which extracellular neurotransmitters function. The aim is to ensure that each microenvironment is optimized for proper neurological function. Along with endothelial cells, astrocytes also form a physical barrier that separates brain and bloodstream. Junctions controlled by astrocytes manage just what passes through and glial cells (a type of astrocyte) maintain the brain as an “immunologically privileged site,” with immune factors excluded from the brain.
However, peripheral immune response (outside of the CNS) may upset that balance. In particular, peripheral inflammation can trigger neuroinflammatory responses that cross the blood–brain barrier (BBB) and involve the neurons and glial cells. When leaky brain syndrome occurs, the BBB is compromised, with the brain’s sensitive environment disrupted and microglia responsible for immune-mediated inflammation activated. Among the varied symptoms of neurological inflammation are weight gain (as metabolism shifts), diabetes, low energy, and mood and cognitive disorders.
It’s worth noting that there are both negative and positive aspects of neuroinflammation. The duration and intensity of such inflammation determines whether immune signals help support, or act against, the central nervous system. Brief, controlled inflammatory responses, such as immune-to-brain signals following infection, tend to be beneficial. After traumatic CNS injury, such signals help improve learning, axonal regrowth, and the recovery of memory,. On the other hand, excessive and maladaptive inflammatory responses generate reactive oxygen species and proinflammatory cytokine protein, and can result in cognitive impairments and less neuronal plasticity.
One way of categorizing these differences is through differentiating microglia, the cells that regulate the CNS immune system, into a trio of classes: the fully activated state, the semi-activated state, and the resting state. In the resting state, microglia are working as a security guard, simply coordinating immune sentry functioning. When semi-activated, microglia generate trophic factor (a growth factor associated with wound healing) but do not produced free radicals that attack one’s own cells.
To continue the analogy of the security officer, they work to protect neurons without misfiring and taking out healthy bystander neurons. When fully activated, microglia generate free-radicals such as nitric oxide, superoxide, and proinflammatory proteins. In marshaling the entire arsenal of the immune system, they inevitably damage some bystander neurons, which can have a cascading effect if the BBB is crossed. Immune system activation over time can result in abnormal neurotransmission and serotonin deficiencies, as well as elevated neurotoxic substance production.
Source: dralirezaminagar
