Monday, 16 May 2011

Don't let me in: the blood-brain barrier

Several of the posts on this blog include the concept of biological barriers and what potentially might be the effects of problems with hyperporosity (leakiness) of such barriers. This is particularly true of the gastrointestinal barrier in relation to things like coeliac disease and inflammatory bowel disease. Autism also seems to figure to varying degrees in such discussions.

The gastrointestinal barrier may well be important for lots of different reasons; predominantly stopping things getting out - fragments of food proteins, peptides, eosinophils, etc. which could conceivably have various somatic effects (and possibly a few psychological ones too).

In this post I want to talk about a barrier which is primarily charged with stopping things getting in - the blood-brain barrier (BBB). I am not going to just recite the various descriptions of the BBB. Suffice to say that it is a partly chemical and partly physical barrier which protects perhaps our most complex organ. The scientific literature extensively discusses the BBB with reference to just about everything - structure, development, disease, etc. With regards to autism, there is also a fair amount of material to analyse.

One might assume some potential relationship between the BBB and some cases of autism given the effect of conditions such as encephalitis and meningitis on barrier function potentially connected to autism onset tied into such infections. The fact that seizures and epileptic syndromes can also affect/be affected by the barrier might also be of some interest given the presence of this fairly common co-morbidity.

Quite a bit of the early autism-BBB material is taken up on peptide-hormone chemistry and in particular the opioid-excess theory of autism. There is still a degree of speculation on this theory with reference to the BBB (not so much the gut membrane), and not everyone is as much a fan as I am of the potential for the theory, but that is perhaps fodder for another post. There are also subtle hints of immune effects to things like cows milk protein potentially tied into 'alterations in the blood-brain barrier' in autism. Although the precise mechanism has yet to be elucidated, inflammation seems to be key, and cytokines might have quite a significant role to play.

Other research has suggested a connection between aberrant amino acid transport across the BBB and autism. Levels of serum tryptophan, for example, have been suggested to be perturbed in some cases of autism with possible implications for levels available for subsequent brain 5-HT synthesis given also the enzyme kinetics linked to the presence of other amino acids.

Our old friend tetrahydrobiopterin (BH4) has also been mentioned with the BBB and autism in mind.
This is an interesting study on the possibility that genetic differences in one or more of the proteins which potentially aid transport of drugs across the BBB might (partially) account for differences in the effectiveness of some medications used for autistic symptoms. I do wonder if similar studies might also shed some light on the different experiences of medication used in autism.

What seems to be missing from the research on the BBB and autism is data on the integrity of the BBB. There are quite a few ways to measure such permeability based on the various drug transport studies around including use of Evans Blue and other contrast agents coupled with MRI.

I assume that research will eventually get round to looking further at the BBB in relation to autism given the current focus on brain structure and autism. I will perhaps come back to the BBB at a later date given its potential importance for lots of things related to autism and beyond.