Glial scars are normally caused by neurodegenerative reactions in the brain, however, the NRHypo neurodegeneration is an exception to this occurrence. Studies of activated microglia and histochemical stains for glial proteins (astrocytes) show that when a lot of the neuronal population in the posterior cingulate cortex is destroyed by an NMDA antagonist, there is an increase in markers for both types of glia. Therefore, the theory that brain alterations in schizophrenia are not associated with gliosis could suggest that changes occurred during developmental stages or by an NRHypo mechanism. 

Glial scarring and its effects of the neurological state of the brain

If the NRHypo state is already there throughout one’s infant and childhood schizophrenic brain, why are psychotic and neurotoxic effects not triggered until adulthood? The NRHypo mechanism explains this question, as it depends on a chain reaction created by a transmitter system interference which then triggers a change in another transmitter  system until it reaches an endpoint. This chain cannot occur unless the entire synaptic connections are in place, 

Schizophrenia and NRHypo disturbances have the same age dependency profile

Evidence supports the claim that a blockade of NMDA receptors can trigger a network disturbance which features the inactivation of particular inhibitory neurons and disinhibition of excitatory pathways. Researchers propose that the same core mechanism and neural network disruption are causes of the neurotoxic and psychotoxic effects of NMDA antagonist drugs. 

Mechanism for how the NRHypo state triggers psychosis and structural brain changes

If hyperstimulation is present in a patient with schizophrenia, it is understandable to suggest that hyperstimulation may have caused psychotic symptoms (alongside no pathological alterations or changeable reactions). If these levels of hyperstimulation are excessive, then it could cause many physical psychotic effects (detectable through brain imaging or even undetectable changes). 

University of Illinois at Chicago

The image below displays the distribution of degenerating neurons at eight different levels of an adult rat brain. These results show how the brain looks 4 days following treatment when exposed to a high dosage of an NMDAThis shows which neuronal populations are most at risk of degeneration when the NMDA receptor system is hypofunctional. 

Representation of the distribution of degenerating neurons

Corso, T. D., & Farber, N. B., et al., (1999, November 29). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research. https://www.sciencedirect.com/science/article/abs/pii/S0022395699000291#:~:text=When%20the%20NMDA%20receptors%20in,hyperstimulate%20the%20primary%20corticolimbic%20neurons.

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