Excitotoxicity and Calcium Dysregulation: How They Affect Brain Cells

When brain cells get hurt or die, two main things are usually involved: excitotoxicity and calcium dysregulation. These problems can play a big role in brain diseases.

1. What is Excitotoxicity?

   • This is when brain cells get damaged because they are overstimulated by a chemical called glutamate.
   • Glutamate connects with specific brain cell receptors, especially NMDA and AMPA receptors.
   • Too much glutamate can happen in situations like stroke, brain injuries, and other brain diseases.
   • Research shows that excitotoxicity can kill up to 70% of brain cells in the areas affected if the receptors are active for too long.

2. What is Calcium Dysregulation?

   • Calcium ions (Ca²⁺) are super important for how cells communicate inside the body.
   • But if there’s too much calcium inside a cell, it can set off reactions that lead to cell death.
   • Normally, calcium levels are carefully controlled, usually staying around 100 nanomoles.
   • However, during excitotoxic events, these levels can spike to much higher amounts (micromolar levels).
   • High calcium levels can cause several harmful effects, such as:
     • Activating enzymes that break down cell membranes.
     • Triggering other enzymes that destroy important proteins in the cell.
     • Hurting mitochondria (the cell’s powerhouses), which can reduce energy and produce harmful molecules called reactive oxygen species (ROS).

3. Some Important Facts:

   • Excitotoxicity is linked to about 50% of brain cell deaths in diseases like Alzheimer’s.
   • In animal studies, blocking NMDA receptors has helped reduce brain cell loss by about 30-50%.

In summary, excitotoxicity and calcium dysregulation are closely connected and play big roles in harming brain cells. Understanding these processes is important for creating new treatments to help protect our brains.