Neuroprotective - Neuropedia


“Neuroprotective” refers to a therapy or substance that helps protect or regenerate cell structure and function within the central nervous system. The nervous system includes the cells, tissues, and structure of the brain and the spinal cord. 

When something is neuroprotective, it helps prevent further degeneration after an injury to the central nervous system.[1]

Events that can cause nervous system injury include:

  • Stroke
  • Accidents
  • Meningitis
  • Brain tumor
  • Encephalitis
  • Medications
  • Subdural hemorrhage
  • Transient ischemic attack

The term neuroprotective can also refer to preventive measures — substances and practices that protect the nervous system from degrading prematurely. Neuroprotective treatments are often designed to limit the loss of function throughout the entire nervous system.[2] 

Oxidative Stress and Neuroprotection

Because oxidative stress is often associated with disorders and degeneration of the central nervous system, neuroprotection often involves limiting damage from oxidative stress. Oxidative stress occurs when there are more reactive oxygen species (ROS) or free radicals than antioxidant defenses, resulting in damage to cells and tissue.[3] 

Oxidative stress has been linked with many neurodegenerative disorders, including:

  • Alzheimer’s disease
  • Parkinson’s disease
  • Huntington disease
  • Lewy body disease

How Does Neuroprotection Work?

Neuroprotection includes many different procedures, therapies, and compounds that help to inhibit cell dysfunction and eventual cell death. In addition to oxidative stress, neuroprotection may counteract other mechanisms of neurodegeneration, including:

  • Apoptosis
  • Excitotoxicity
  • Myelin dysfunction
  • Mitochondrial dysfunction

More recently, neuroprotection has also been studied for its role in treating neuropsychological disorders such as mood disorders, multiple sclerosis, schizophrenia, and epilepsy.[4] 

Free Radicals Definition

Free radicals are oxygen-containing molecules with at least one unpaired electron in their outer shell. This uneven number makes them “unstable” and causes them to react more easily with other molecules. Free radicals (also called reactive oxygen species) can trigger damaging chemical reactions in the body known as oxidation.[5]

Free radicals are naturally generated by the body, but are exacerbated by certain chemicals, toxins, stress, illnesses, and more. While too much free radical damage can result in cell and tissue damage, a certain number of free radicals are natural and harmless. Free radicals can even fight off pathogens that cause disease. [6] It is necessary, however, for a balance of free radicals and antioxidants in order to maintain proper physiological function.[7]

The Free Radical Theory of Aging

The prevailing theory is that when free radicals outnumber antioxidants in the body, they build up. This causes damage to healthy cells. Scientists believe that this, in turn, is how aging happens and diseases like cancer develop.[8]  

Free radicals can injure many types of cells, including DNA, proteins, and lipids. The damage that they produce to cells is called oxidative stress.[9] 

This damage is often a kind of chain reaction, due to the instability of the free radical. In an attempt to stabilize itself, the free radical takes an electron from the outer shell of a complete molecule, which in turn leaves that molecule without a full outer shell — creating another free radical that is now looking to stabilize itself by stealing an electron from another molecule. Antioxidants are thought to stop this chain reaction by donating an electron to the free radical without becoming one themselves.[10] 

Free radicals vs. reactive oxygen species

Sometimes, the term free radical and reactive oxygen species are used interchangeably. However, this isn’t quite accurate. Reactive oxygen species are considered the most “biologically significant” free radicals.[11] 

Reactive Oxygen Species Definition

Reactive oxygen species is the term used to describe the group of free radical and non-radical molecules that contain oxygen. They are also referred to as oxygen radicals, reactive oxygen intermediates, and reactive oxygen metabolites. Reactive oxygen species are produced by cells when the body uses oxygen. Their production can also be stimulated in response to environmental stressors like air pollution or heavy metals. [12]  

Some examples of receive oxygen species include: 

  • Ozone (O3)
  • Hydrogen peroxide (H2O2)
  • Singlet oxygen (1O2)
  • Lipid hydroperoxide (LOOH)
  • Hypochlorous acid (HOCl)
  • Hydroxyl radical (OH▪)
  • Peroxyl radical (LOO▪)
  • Alkoxyl radical (LO▪)
  • Superoxide (O2▪−)
  • Peroxynitrite (ONOO−)[13]

Functions of reactive oxygen species

Reactive oxygen species perform important functions in the body. They signal cells to mount an inflammatory response to pathogens. They also influence autophagy, the process of clearing out cells that have become damaged or dysfunctional.[14] 

However, it is believed that when levels of reactive oxygen species are so high that they are unable to be countered by antioxidants within the body, cell damage called oxidative stress can occur. [15],reactive%20oxygen%20species%20(ROS)[16] This cell damage is believed to play a role in the development of diseases, including cancer[17], high blood pressure[18], and neurodegenerative diseases like Parkinson’s and Alzheimer’s.[19] 

Reactive oxygen species also appear to play a part in the proliferation of tumors, according to studies in rodents.[20] They have also been studied for their negative impact on male fertility.[21]   

What’s the difference between reactive oxygen species and free radicals?

The terms free radical and reactive oxygen species are often used to denote the same thing; however reactive oxygen species are a type of free radical and they do not have to be a radical. Some reactive oxygen species have a stable outer shell of electrons.[22] 

Antioxidant Definition

Antioxidants are natural or artificial substances that work to protect cells from damage caused by free radicals and the adverse effects they can produce in the human body. Antioxidants are found in abundance in many fruits and vegetables. 

Examples of antioxidants:

  • Vitamin E
  • Vitamin C
  • Selenium
  • Lycopene
  • Beta-carotene
  • Lutein

Since antioxidants can help to neutralize free radicals, and free radicals are thought to contribute to the development of disease, many researchers believe that increased consumption of antioxidants should, in turn, help combat disease.[23] 

The role of antioxidant supplements

However, antioxidant supplementation alone may not provide the expected health benefits. One long-term, high-quality study determined that vitamin E supplements did not help to prevent heart problems or cancer in women.[24]  Another study in men originally showed that supplementation with vitamin E and selenium did not prove beneficial in preventing prostate cancer. Follow-up years later suggested that vitamin E supplements actually increased the risk of prostate cancer in this same group of men. [25] 

In contrast, the Age-Related Eye Disease Study found that when participants combined beta-carotene, vitamin E, and vitamin C, the risk of development of age-related macular degeneration significantly declined.[26] 

It appears as though regular consumption of fruits and vegetables is likely most beneficial when it comes to health.[27]  

Some foods with high levels of antioxidants: ​​

  • Teas
  • Herbs
  • Spices
  • Berries
  • Greens
  • Root vegetables
  • Winter squashes
  • Cruciferous vegetables[28] 

Oxidative Stress Definition

Oxidative stress is the process of cellular damage that occurs when free radicals and reactive oxygen species interact with biological molecules like DNA, lipids, membranes, or proteins. Oxidative stress is thought to be the root of aging, and a driver of disease. 

Conditions thought to be related to oxidative stress:

  • Cancer
  • Kidney disease
  • Respiratory disease 
  • Rheumatoid arthritis
  • Neurological disease
  • Cardiovascular disease

Oxidative stress occurs when levels of free radicals and reactive oxygen species accumulate to the point that antioxidants can not keep them in check.[29] 

What are free radicals?

Free radicals are molecules that have an incomplete, unstable outer shell of electrons. This makes them seek out other complete molecules and steal an electron in their outer ring. Once that happens, the molecule is left with an incomplete outer shell and is then a free radical itself. This chain reaction eventually ends in cellular damage. 

Antioxidants are able to step in and put a halt to this process by donating an electron to the free radical without turning into a free radical.[30] 

This is why many scientists describe oxidative stress as an imbalance between free radicals and antioxidants.

It is also why researchers have studied the role that increasing antioxidant intake can play in preventing disease. In theory, if antioxidants can combat free radical damage, then increasing the number of them in the body should prevent a situation where imbalance can occur — thereby slowing the aging process and potentially even preventing disease.[31] 

Inflammation Definition

Inflammation is the body’s protective response to injury, irritation, or pathogens (germs like bacteria, fungi, or viruses). Inflammation can also be triggered by exposure to radiation or certain chemicals. Inflammation can be acute or chronic.

Acute inflammation has 5 classic symptoms: 

  • Pain 
  • Heat
  • Swelling
  • Redness
  • Impaired function[32]  

What is acute inflammation?

Acute inflammation occurs when the immune system response is triggered by a specific and localized threat to the body. This type of inflammation can help to resolve injuries and infections within a limited time frame. Acute inflammation may result in increased blood flow, dilated blood vessels, and fever.[33]  

What is chronic inflammation?

Chronic inflammation, also known as low-grade inflammation, happens when the body mounts an immune response over an extended period of time. Chronic inflammation is said to be a marker of disease. When the body is experiencing chronic inflammation, the symptoms are less obvious than those of acute inflammation. Symptoms of chronic inflammation are sometimes considered “invisible” because they don’t produce heat or swelling as acute inflammation does.[34] 

Chronic inflammation is associated with several diseases, including cancer[35] and heart disease.[36] Studies suggest that a healthy diet[37] and exercise [38] may help reduce levels of chronic inflammation in the body. 

What is autoimmune disease?

When the inflammatory response is mistakenly directed towards an otherwise healthy body part, this is called autoimmune disease. This chronic inflammation can lead to organ and tissue damage.[39] 

There are over 100 known autoimmune conditions. Common autoimmune diseases include: 

  • Lupus
  • Fibromyalgia
  • Celiac disease
  • Type 1 diabetes
  • Rheumatoid arthritis
  • Hashimoto’s thyroiditis
  • Inflammatory bowel disease (IBD)[40]