The Black Substance and Dopamine

The substantia nigra is located in the midbrain of the brainstem. The midbrain is the highest portion of the brain stem. In the picture below in the upper left corner, their location is indicated by the red line. The location of the midbrain is more clearly seen in the larger picture below in the indentation just above the protruding belly of the pons. (See the grey structures above the red area.)

The midbrain connects to the diencephalon of the brain above, which contains the thalamus and hypothalamus of the brain. On the bottom side it connects to the pons, which is connected to the lowest point of the brainstem called the medulla oblongata. In addition to linking the midbrain to the medulla, the pons also connects to the cerebellum, hence it’s name comes from the latin word for bridge. At the bottom of the braintem, the medulla connects to the cord.

Substantia nigra means black substance. It was so named because of its black appearance on microscopic examination. The substantia nigra produces and uses dopamine, which is a chemical that crosses the gap between nerves to connect and stimulate them. Dopamine is just one of many different types of the connecting chemicals that are collectively called neurotransmitters. While dopamine plays a prominent role in Parkinson’s disease, it plays a far more important role in brain function than simply physical movement. I discuss the role of dopamine further in my book and will do so on this website as it expands.

Cisterns, Central Aqueduct and CSF in Brainstem Compression

The role of degeneration of the substantia nigra and the subsequent decrease in the production of dopamine in Parkinson’s disease is well documented. The cause of the slow or sometimes sudden demise of such as small segment of the brain, however, remains a mystery. What could cause such a small area to malfunction and decrease its production of dopamine with no apparent explanation and nothing visible to the eye? Many theories have been suggested including genetics, but one of the most likely theories, that has yet to be investigated, is increased CSF volume and pressure in the cisterns surrounding the brainstem and the cerebral aqueduct that passes through it.

The cisterns are enlargements in the subarachnoid spaces, which contain cerebrospinal fluid (CSF) that surrounds the brainstem and cerebellum.(see picture below) One of the primary purposes of the cisterns is to maintain the proper position of the brainstem and cerebellum inside the cranial vault and to protect them from compression against the bones of the base of the skull. One of the cisterns, called the interpeduncular cistern is located at the top of the brainstem above the belly of the pons and in front of the midbrain. Keep in mind, the midbrain contains the substantia nigra.

The cerebral aqueduct lies in the middle of the midbrain. The central aqueduct is a canal for the passage of cerebrospinal fluid (CSF) from the third ventricle above, in the brain, to the fourth ventricle below located in the brainstem. When CSF backs up it most likely fills the subarachnoid spaces first. Since the cisterns are enlargements in the subarachnoid spaces strategically located toward the bottom of the brain and brainstem, due to gravity, they most likely fill first. As the cisterns back up the next likely place to back up is the fourth ventricle followed by the cerebral aqueduct, followed by the third and lastly, the lateral ventricles which are the highest.

In this regard, the substantia nigra is in the unfortunate position of getting potentially squeezed by an increase in CSF volume in either the cisterns or the central aqueduct, or it could get squeezed by both. Moreover, Parkinson’s disease has been associated with normal pressure hydrocephalus (NPH).

It seems likely that certain cases of Parkinson’s disease may be due to low level NPH without enlargement of the ventricles; therefore the connection goes unrecognized because of our current definition of hydrocephalus, which requires enlargement of the ventricles called ventriculomegaly.

On the other hand, some scientists suggest that hydrocephalus should include any condition that causes a back up in CSF flow. In the meantime, upright Cine MRI studies of CSF flow are continuing to unlock the mystery of Parkinson’s, NPH and other neurodegenerative conditions caused by poor blood and CSF flow in the brain.