Strategy 2: Make the tissue more resilient to poor plumbing. Pros: Likely a pharmacological treatment Can be administered more quickly by 1 st response team Can extend therapeutic time window. May be of benefit to a large number of people. Cons: - Does not exist. How to treat stroke.
Maybe, just maybe, it’ll work…
Reduce need for energy (ATP), reduce synaptic glutamate release.
“Shut the patient down”, do not prevent non-synaptic glutamate release, systemic toxicity (cardiovascular).
Na channel blockers currently not in use. Clinical trials have shown no utility. Quaternary local anesthetics may be of utility, however currently experimental
K+ channel openers have found utility in chronic spinal cord injury. Phase III trials ongoing for stroke treatment.
Block presynaptic calcium entry
Obviously not an immediate solution.
First used in neuorlogical diseases by Dr. Temple Fay, in the mid-late 1930’s
Agents that block postsynaptic receptors.
General anesthetics are considered by some to be neuroprotective.
Inhalational anesthetics may confer protection during neurosurgery (controversial).
Most commonly used are the IV anesthetics Barbiturates (activate GABA), propofol (activates GABA, blocks NMDA), ketamine (blocks NMDA).
Barbiturates and propofol commonly used in neurosurgery for brain protection.
Free radical scavengers
Nitric Oxide Synthase antagonists
Inhibitors of other intracellular enzymes (protein kinases, phosphatases)
There are a few ways in which glia cells are different from neurons:
1. Neurons have TWO "processes" called axons and dendrites....glial cells only have ONE.
2. Neurons CAN generate action potentials...glial cells CANNOT. However, glial cells do have a resting potential.
3. Neurons HAVE synapses that use neurotransmitters...glial cells do NOT have chemical synapses.
4. Neurons do not continue to divide...glial cells DO continue to divide.
5. There are many MORE (10-50 times more) glial cells in the brain compared to the number of neurons.
More numerous than neurons
Have many different functions
Scavengers (immunological role)
Tight junctions (Blood-Brain Barrier)
Oligodendroglial cells express AMPA subtype of glutamate receptors.
Oligodendroglia are the white matter cell most susceptible to excitotoxicity in anoxic injury.
Li S, Mealing GA, Morley P, Stys PK
J Neurosci 1999 Jul 15;19(14):RC16