Refers to the relative preservation of neuronal structure and/or function.

In the case of an ongoing neurodegenerative insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time.

A proposed treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, and spinal cord injury.

Injuries associated with CNS disorders include increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation.

Neuroprotective treatments often target oxidative stress and excitotoxicity with glutamate antagonists and antioxidants,

Glutamate excitotoxicity is an important mechanisms to trigger cell death in CNS disorders.

Over-excitation of glutamate receptors allows for an increase in calcium ion influx, and because Ca2+ is a secondary messenger and regulates a large number of downstream processes its accumulation of causes improper regulation of these processes leading to cell death.

Ca2+ considered a trigger of neuroinflammation, a key component in all CNS disorders.

Glutamate antagonists inhibit the binding of glutamate to NMDA receptors such that accumulation of Ca2+ and therefore excitotoxicity can be avoided.

17β-Estradiol helps regulate excitotoxicity by inhibiting NMDA receptors as well as other glutamate receptors.

Ginsenoside Rd attenuates glutamate excitotoxicity.

Progesterone can prevent secondary injuries in patients with traumatic brain injury and stroke.

Simvastatin in models of Parkinson’s disease have neuroprotective effects including anti-inflammatory effects due to NMDA receptor modulation.

Neuroinflammation is associated with cerebral ischemia as well as many neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, and Amyotrophic Lateral Sclerosis.

Oxidative stress causes neuron apoptosis.

Oxidative stress causes neuron cell death directly or lead to protein misfolding, proteasomal malfunction, mitochondrial dysfunction, or glial cell activation.

Each of these events causes neuron cell apoptosis, and by decreasing oxidative stress through neuroprotective treatments, further neurodegradation can be inhibited.

Antioxidants are the primary agents used to control oxidative stress levels.

Antioxidants aim to eliminate reactive oxygen species, which are the prime cause of neurodegradation.

Antioxidant effectiveness in preventing neurodegradation depends on the underlying disease process, gender, ethnicity, and age.

Common antioxidants shown to be effective in reducing oxidative stress in neurodegenerative disease:

Acetylcysteine: targets glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways.

Crocin which is derived from saffron is a potent neuronal antioxidant.

Estrogen: 17α-estradiol and 17β-estradiol are effective as antioxidants.

Fish oil: This contains n-3 polyunsaturated fatty acids that offset oxidative stress and mitochondrial dysfunction.

Minocycline: is a strong antioxidant and has broad anti-inflammatory properties, and has been shown to have neuroprotective activity in the CNS for Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, and ALS.

Pyrroloquinoline quinone (PQQ) as an antioxidant has multiple modes of neuroprotection.

Resveratrol prevents oxidative stress by attenuating hydrogen peroxide-induced cytotoxicity and intracellular accumulation of ROS, and exerts protective effects in multiple neurological disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and ALS as well as in cerebral ischemia.

Vinpocetine exerts neuroprotective effects in ischemia of the brain through actions on cation channels, glutamate receptors, decreases dopamine and may contribute to its protective action from oxidative injury, has


anti-inflammatory affects and may be beneficial for the treatment of neuroinflammatory diseases.

Vinpocetinine increases cerebral blood flow and oxygenation.

Vitamin E has had varying responses as an antioxidant and is most effective in Alzheimer’s disease, but is ineffective for neuroprotection in Parkinson’s disease.

NMDA receptor stimulants can lead to glutamate and calcium excitotoxicity and neuroinflammation.

Selegiline slows early progression of Parkinson’s disease and delays the emergence of disability by an average of nine months.

Nicotine delays the onset of Parkinson’s disease.

Caffeine has a protective effect against Parkinson’s disease.

Caffeine induces neuronal glutathione synthesis leading to neuroprotection.

Therapeutic hypothermia in traumatic brain injury helps reduce intracranial pressure.

Erythropoietin protects nerve cells from hypoxia-induced glutamate toxicity.

Lithium exerts neuroprotective effects and stimulates neurogenesis by inhibiting glycogen synthase kinase-3 (GSK-3), upregulates neurotrophins and growth factors, modulates inflammatory molecules, upregulates neuroprotective factors, heat shock protein 70 and concomitantly downregulates pro-apoptotic factors.

Lithium reduces neuronal death, microglial activation, cyclooxygenase-2 induction, amyloid-β (Aβ), and hyperphosphorylated tau levels, to preserve blood-brain barrier integrity, to mitigate neurological deficits and psychiatric disturbance, and to improve learning and memory outcome.

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