Brain Protection in Schizophrenia, Mood and Cognitive Disorders by Michael S. Ritsner

Author:Michael S. Ritsner
Language: eng
Format: mobi
Publisher: Springer
Published: 2010-07-31T21:00:00+00:00

12

Is a Neuroprotective Therapy Suitable for Schizophrenia Patients?

355

Thus, currently schizophrenia is best conceptualized as a “multiple hit” illness or

spectrum disorder similar to cancer.

12.3 Neuroprotective Approach

The neuroprotective approach is a treatment paradigm, that is theoretically based

on both neurodevelopmental and neurodegenerative models of schizophrenia. This

approach aims to protect against gray matter loss and slow functional decline fol-

lowing the onset of psychosis, and to maintain functional integrity of the brain in

response to neurobiological stress. Neuroprotective therapy is the administration of

an agent (medication, compound etc.) that can reverse some of the damage or pre-

vent further damage. By definition, neuroprotection is an effect that may result in

salvage, recovery or regeneration of the brain, its cells, structure and function [46,

85–88].

During the past few years research has focused on developing neuroprotec-

tive agents for the therapy of various degenerative diseases, including Alzheimer’s

disease, amyotrophic lateral sclerosis, Parkinson’s disease, and glaucoma [89].

Regarding schizophrenia and related disorders some neuroprotective agents (e.g.,

erythropoietin, glycine, D-serine, neurosteroids, memantine, celecoxib, and others)

are currently being evaluated as add-on therapies. Ehrenreich et al. [90] reviewed the neuroprotective approach using erythropoietin that represents a novel frontier. The

“Gottingen EPO-stroke trial” represents the first effective use in man of a neuropro-

tective therapy in an acute brain disease.The experimental erythropoietin therapy

to combat cognitive decline in patients with schizophrenia was introduced as a

neuroprotective strategy for a chronic brain disease. There is ample evidence that

neurotrophins and endogenous cannabinoid systems have numerous neuroprotective

effects (see below).

12.4 Targets for Neuroprotective Therapy

Although the molecular mechanisms of neurodegeneration and pathogenesis of

schizophrenia remain largely unknown, a significant body of literature indicates

that the main mechanisms implicated in the disease process may include apoptosis,

excitotoxicity, oxidative stress, stress and others.

12.4.1 Apoptosis

Apoptosis (programmed cell death) is a normal physiologic process that occurs

during embryonic development as well as in the maintenance of tissue home-

ostasis. Studies have shown that various neurochemical events at the synapse can

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