Cumulative multiple early life hits- a potent threat leading to neurological disorders

Early life Stress is a worldwide concern linked with development of later life neurological disorders. Early developmental age is sensitive to many prominent environmental insults like malnourishment, immune inflammation, abuse, maternal separation, alcohol and drugs. Hence, an individual during an early age encounters more than one simultaneous stressor that leads to impairment of cognitive and behavioral abilities, a symptom common to most of the neurological disorders. Stressors like malnourishment and immune inflammation are common and encountered by a huge number of populations, contributing enormously to a damaged CNS and in most of the cases they act synergistically in dependency to each other, giving rise to the concept of multi-hit. Multi perinatal hit acts by mimicking the mechanism of ageing in CNS and increasing the risk for later life neurological disorders. Multi stress exposure is also responsible for disrupting the cellular homeostasis of the brain by inducing glial activation, neurotoxicity and oxidative stress, which is the major reason of cell death and circuitry damage in brain. Multi perinatal hit thus increases the risk of neurological disorders by many folds through interfering with ongoing developmental cascades and eventually modulating the fate of cellular components in brain. Thus, a stress induced architecturally and chemically altered CNS is vulnerable and prone to neurological disorders like Alzheimer's, Schizophrenia, ALS, Autism and Parkinson's disease. This review compiles the information available regarding the effects of early life stressors on different components of brain, primarily focusing on the connection between perinatally encountered multi hit and development of later life neurological disorders.