The blood-brain barrier

The human brain, which weighs about 2% ^[137] of the body's mass, requires more than 20% ^[138] of the total body's energy supply; thus, it alone receives 16% ^[5] of the arterial irrigation.

The CNS has no real reserves of energy or oxygen ^[109], and neurons are incapable of functioning anaerobically ^[52]. It is therefore an organ entirely dependent on continuous perfusion and a sufficient supply of oxygen and nutrients. Consequently, after 10 seconds without oxygen, consciousness is lost, and after a few minutes, neurons begin to die ^[105].

Conversely, the nervous system requires a stable environment for optimal functioning. It cannot tolerate massive and sudden fluctuations in molecular and ionic composition within the interstitial spaces. For this reason, the nervous system is almost totally isolated from the blood by a barrier that acts as a mandatory and extremely selective filter between the contents of the capillaries and the extracellular environment of the nervous tissue. This barrier is called the blood-brain barrier ^{[41, 70]} (BBB).

Before the discovery of microglia and their immune role within the CNS, it was thought that the latter relied on the blood-brain barrier as its only means of passive defense against toxic and infectious attacks.

Anatomy:

The BBB consists of three essential elements ^[70]:

The tight junctions of the endothelial cells that line the interior of the blood capillaries. In the brain, these junctions have a structure that is significantly more impermeable than in the rest of the body, and the number of mitochondria in these endothelial cells is 5 to 10 times higher than elsewhere ^[91]; this is a response to the very high energy demand of active transport processes at this level.

The basal membrane of the arterial capillaries.

The astrocytic end-feet of type I astrocytes ^{[41, 70]} form (by joining together) a continuous sheath that serves as a selective barrier against the entry of pathogens and neurotoxic substances into the nervous tissue."

Physiology:

In addition to their relatively passive participation in the formation of the blood-brain barrier, astrocytes are also capable of controlling the contraction and dilation of blood vessels ^[96], thereby regulating blood flow to manage the uptake of substances according to needs.

The blood-brain barrier plays both a physiological and an anatomical role; gases (oxygen and carbon dioxide), as well as fat-soluble substances and alcohol ^[91], can freely cross it according to their concentration gradient (from higher to lower concentration). In contrast, polar molecules (ionized, hydrophilic) can only diffuse through active transport mechanisms involving specific channels and pumps, which operate only according to requirements.

Therapeutics:

The blood-brain barrier constitutes a real obstacle to the passage of drugs ^[41] targeting neurological conditions such as brain tumors. Several research projects are currently being conducted to address this problem.

This constraint can be bypassed either by the injection of high doses of drugs, the administration of an agonist or a precursor that crosses the barrier (as in the case of L-dopa vs. dopamine ^{[1, 41]}), or by the intrathecal injection ^[42] of the drug (directly into the CSF).

Pathology:

In newborns and infants, the blood-brain barrier is not as effective as in adults; it allows the passage of certain neurotoxic molecules, such as bile pigments, which can damage the brain (kernicterus) ^[42].

In certain pathological cases, such as meningitis, there is a breakdown of the BBB, which fortunately facilitates the passage of antibiotics, such as penicillin, into the central nervous system ^[42].