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

Recent evidence provides insufficient evidence of neuroprotective strategies to guide clinical management, and more randomized clinical trials are needed to optimize patient care 1).

In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation.

It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, and spinal cord injury. Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons.

Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms include increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation.

Of these mechanisms, neuroprotective treatments often target oxidative stress and excitotoxicity—both of which are highly associated with CNS disorders. Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own.

Thus limiting excitotoxicity and oxidative stress is a very important aspect of neuroprotection. Common neuroprotective treatments are glutamate antagonists and antioxidants, which aim to limit excitotoxicity and oxidative stress respectively.

Great expectations have been raised about neuroprotection of therapeutic hypothermia in patients with traumatic brain injury (TBI) by analogy with its effects after heart arrest, neonatal asphyxia, and drowning in cold water.

Some drugs such as corticosteroids and progesterone have already been investigated in TBI neuroprotection but failed to demonstrate clinical applicability in advanced phases of the studies. Dietary antioxidants, such as curcumin, resveratrol, and sulforaphane, have been shown to attenuate TBI-induced damage in preclinical studies. These dietary antioxidants can increase antioxidant defenses via transcriptional activation of NRF2 and are also known as carbonyl scavengers, two potential mechanisms for neuroprotection 2).


see Hypothermia.


Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate (VPA) exhibits neuroprotective effects in animal models. However, humans cannot tolerate high doses of VPA.

A study found that 30 mg/kg of VPA assists in treating TBIs in rat models 3).

Neuroprotection of the spinal cord during the early phase of injury is an important goal to determine a favorable outcome by prevention of delayed pathological events, including excitotoxicity, which otherwise extend the primary damage and amplify the often irreversible loss of motor function. While intensive care and neurosurgical intervention are important treatments, effective neuroprotection requires further experimental studies focused to target vulnerable neurons, particularly motoneurons.

The mechanism of the protective competence of nimodipine is unknown. Therefore, a study, we established an in vitro model to examine the survival of Neuro2a cells after different stress stimuli occurring during surgery with or without nimodipine. Nimodipine significantly decreased ethanol-induced cell death of cells up to approximately 9% in all tested concentrations. Heat-induced cell death was diminished by approximately 2.5% by nimodipine. Cell death induced by mechanical treatment was reduced up to 15% by nimodipine. These findings indicate that nimodipine rescues Neuro2a cells faintly, but significantly, from ethanol-, heat- and mechanically-induced cell death to different extents in a dosage-dependent manner. This model seems suitable for further investigation of the molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine 4).

Melatonin appears to have neuroprotective effects on the secondary brain damage while nimodipine and nimodipine plus melatonin combination did not show such neuro-protective effects on the secondary brain injury 5).

see Methoxyflurane.

Erythropoietin and curcumin showed promising neuroprotective effects in various models of Alzheimer's dementia.

Badenes R, Gruenbaum SE, Bilotta F. Cerebral protection during neurosurgery and stroke. Curr Opin Anaesthesiol. 2015 Oct;28(5):532-6. doi: 10.1097/ACO.0000000000000232. PubMed PMID: 26308509.
Mendes Arent A, de Souza LF, Walz R, Dafre AL. Perspectives on Molecular Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain Injury. Biomed Res Int. 2014;2014:723060. Epub 2014 Feb 13. Review. PubMed PMID: 24689052.
Tai YT, Lee WY, Lee FP, Lin TJ, Shih CL, Wang JY, Chiu WT, Hung KS. Low dose of valproate improves motor function after traumatic brain injury. Biomed Res Int. 2014;2014:980657. doi: 10.1155/2014/980657. Epub 2014 Feb 6. PubMed PMID: 24689067.
Herzfeld E, Strauss C, Simmermacher S, Bork K, Horstkorte R, Dehghani F, Scheller C. Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model. Int J Mol Sci. 2014 Oct 14;15(10):18453-18465. PubMed PMID: 25318050.
Ismailoglu O, Atilla P, Palaoglu S, Cakar N, Yasar U, Kilinc K, Kaptanoglu E. The therapeutic effects of melatonin and nimodipine in rats after cerebral cortical injury. Turk Neurosurg. 2012;22(6):740-6. doi: 10.5137/1019-5149.JTN.6197-12.1. PubMed PMID: 23208906.
  • neuroprotection.txt
  • Last modified: 2016/02/01 16:49
  • (external edit)