Status Epilepticus, TLE, and GABA-A Receptor Gene Therapy

Temporal lobe epilepsy (TLE) refers to a condition where recurrent seizures arise in the temporal lobe of the brain. This condition is seen in humans and animals. Often, TLE arises following a neural insult such as head trauma or tumor, but can also be triggered by infection. These febrile seizures are often seen in children under the age of five, and subsequent scans can show atrophy of temporal lobe structures such as the hippocampus. The hippocampus is highly interconnected with other temporal lobe structures, so a seizure that originates from or propagates through the hippocampus is likely to result in widespread seizure activity.
While febrile convulsions of short duration (on the order of a few minutes) are somewhat normal in infants, convulsions lasting more than one hour indicate a high risk for developing TLE in the future. TLE resulting in status epilepticus (SE) is of particular concern, as SE is a life-threatening condition where the brain enters a state of persistent seizure, either from one long episode or a series of recurring episodes. Medication may not be effective at controlling SE, and complications are almost inevitable. If SE is the result of TLE, resection of the entire temporal lobe can be successful at eliminating seizure activity. While the brain is very “plastic” in younger children who can recover from this sort of surgery and go on to live almost completely normal lives, such drastic surgery is not desirable as age increases because the brain’s ability to compensate for the surgery is diminished.
With this in mind, I turn your attention to a recent publication.

Everybody Post About Mirror Neurons!!!

Mixing Memory brings up some excellent points regarding mirror neurons in primates, and Frontal Cortex follows up with his thoughts. To both of them I say “bravo, but your skepticism probably doesn’t go far enough”.
We give Rizzolatti et al too much credit with their conclusions. After all, they’ve only demonstrated the existence of mirror neurons in monkeys. Due to the obvious inherent difficulties associated with recording from human neurons in vivo, no one has yet (to my knowledge) published anything that demonstrates the existence of mirror neurons in people. Instead, we stick people in scanners and infer that they have mirror regions, or mirror neural systems, that are at least in part composed of mirror neurons. These regions are associated with language and imitation, but any evidence that mirror neurons are involved with either behavior in humans is circumstantial at best.

Stem Cells for Spinal Cord Injuries

The difficulty with treating spinal cord injuries arises from a number of factors. Firstly there is the primary damage to the axons of the spinal cord itself, resulting in mechanical damage that can inhibit neurotransmission and transport of cellular material to and from the distal cord. The damaged cord must also compensate for secondary damage such as the generation of free radicals, a lack of oxygen to the affected area (anoxia), glial scarring, and a host of other issues.

Pesticide-induced dysfunction of dopaminergic neurons

Shelley mentioned a study last week that suggested more and more young people are getting Parkinson’s Disease, and she wondered whether there was any utility in blaming our industrialized society based on the fact that certain compounds we produce can induce Parkinsonian symptoms. Let’s start by giving a brief overview of the systems involved before we attempt to answer that question.
The substantia nigra contains a collection of dopaminergic neurons that project to the striatum. Integrity of this pathway is essential for normal motor function, although this nigrostriatal system is capable of compensating for cell loss until it loses around 80% or more of its neurons. Loss of these neurons is one of the central features of Parkinson’s Disease, which for the most part has no known cause (idiopathic PD). There are some notable famous exceptions such as the boxer Muhammed Ali who likely had his triggered from repeated blows to the head, and a set of cases that developed in individuals exposed to MPTP, a byproduct of a street chemist’s failed attempt to produce a Demerol-like compound. MPTP is metabolized into MPP+, which is toxic to dopaminergic neurons and can cause a human to basically develop a PD-like disease after a few days of exposure.
Interestingly, some herbicides are now under scrutiny for a potential causal role in PD. One such example is Paraquat, which has a structure similar to that of MPP+

SIRT1 Pathways and the Prevention of Alzheimer’s Pathology

A highly conserved set of genes known as the sirtuin family are known to be activated by caloric restriction (CR) and extend the lifespan of a number of species. CR may also reduce the risk of Alzheimer’s Disease, and can prevent the formation of amyloid plaques in transgenic mouse models of AD. The question, then, is whether sirtuin gene activation is a mechanism through which CR can prevent AD pathology, and what genes/compounds are involved in this particular biochemical cascade. Since I’m writing this post, you can probably guess that I’ve found an article that addresses this very question….

PDE-5 Inhibitor Sildenafil Improves Cognition, or Viagra’s Good for the Big Head Too

Inspired by Rush Limbaugh’s apparent erectile dysfunction, I decided that today’s Evil Journal Club should address the “other” potential uses of PDE-5 inhibitors, the most (in)famous of which is Viagra.

And when you’re in your bigger room…

…you might not know what to do
you might have to think of
how you got started
sittin’ in your little room
–The White Stripes