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The blood-brain barrier is a set of cells lining the blood vessels of the brain and nerves that prevent certain molecules that would otherwise be able to penetrate cells in the body from passing from the blood to the cerebrospinal fluid. These cells prevent the passage of microscopic objects like bacteria, as well as large molecules and molecules that attach easily to water. However, it freely allows the passage of molecules that do not attach easily to water (such as oxygen, carbon dioxide, and hormones) and also actively allows the passage of glucose and some essential proteins.

This effect was first discovered by Paul Ehrlich, who noticed that dye injected into animals was never seen in the brain. However, he did not understand the significance of the lack of dye, putting it down to a poor affinity between the dye and brain tissue. However, one of his students later injected dye directly into the cerebrospinal fluid and noted the brain did take up the dye.

One of the benefits of the barrier is that bacterial infections of the brain and spinal fluid are very rare. However, the flip side of this is that most common pharmaceuticals cannot breach the barrier either and infections of the brain are difficult to treat with normal therapy. Moreover, viruses have no difficulty breaching the barrier. However, when the brain is inflamed, drugs and antibodies can more easily penetrate the barrier. In addition, there are several bacteria that can penetrate the barrier, such as Syphilis and Lyme disease, which can literally tunnel between the bloodstream and the nervous system. Other diseases, such as meningitis, epilepsy, multiple sclerosis, and Alzheimer's disease can affect how the barrier works.

One of the reasons to perform a lumbar puncture is to see if there is one of these rare infections in the spinal fluid, which can narrow down the list of possible diagnoses.

In several episodes, the barrier takes on significance. In Paternity, the patient's condition could only be treated by injecting drugs into the cerebrospinal fluid, which posed the danger of putting too much pressure on the brain. In Cane and Able, a radioactive tag fails to penetrate the barrier to allow the team to find alien brain cells in the patient, leaving him suffering from vivid hallucinations.

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