Glioblastoma: Osmosis Knowledge Shot

Rishi Desai, MD, MPH


October 09, 2019

On August 25th, 2018, US Senator John McCain died after battling with glioblastoma. But what is a glioblastoma, and what makes it so deadly? First, let's zoom out and look at brain tumors in general.

Adult brain tumors are masses of abnormal cells that generally occur in adults and result from the uncontrolled growth of those cells within the brain.

Okay, let's start with some basic brain anatomy. First off, there's the cerebral cortex, which is the part of the brain that's supratentorial, or above the tentorium, and the cerebellum, which is infratentorial or below the tentorium. And the brain has four interconnected cavities called ventricles, which are filled with cerebrospinal fluid—a fluid that helps provide buoyancy and protection, as well as metabolic fuel for the brain. Highest up are two C-shaped lateral ventricles that lie deep in each cerebral hemisphere. The two lateral ventricles drain their cerebrospinal fluid into the third ventricle, which is a narrow, funnel-shaped, cavity at the center of the brain. The third ventricle makes a bit more cerebrospinal fluid and then sends all of the cerebrospinal fluid to the fourth ventricle via the cerebral aqueduct. The fourth ventricle is a tent-shaped cavity located between the brainstem and the cerebellum. After the fourth ventricle, the cerebrospinal fluid enters the subarachnoid space, which is the space between the arachnoid and pia mater, two of the inner linings of the meninges, which cover and protect both the brain and spine. So this makes it possible for cerebrospinal fluid to also flow through the central canal of the spine.

Supratentorial tumors make up the majority of adult brain tumors. A common one is a type of astrocytoma called a glioblastoma. Because astrocytes are found through the brain and spinal cord, astrocytomas can form in all of these locations, but glioblastomas are mostly in the cerebral hemispheres. And while astrocytomas can be graded I through IV, glioblastomas are only grade IV because they are highly malignant tumors. Because of their quick growth and invasion of nearby tissues, glioblastomas tend to rapidly cross the corpus callosum. The corpus callosum is the midline structure that separates the two cerebral hemispheres that looks like a characteristic "butterfly" on a cross-section of the brain. Cancer cells typically recruit blood vessels to provide them nourishment in a process called angiogenesis, but glioblastomas proliferate so fast that even with angiogenesis their nutrient demand outpaces the blood supply.

Treating glioblastoma is particularly difficult because the tumor cells don't die with conventional therapies. To make matters worse, the tumor often spreads out making surgical resection harder, and the blood-brain barrier prevents many medications from accessing the tumor. In general, there's usually a poor prognosis, and treatment with surgery, radiation therapy and chemotherapy is generally used to ease symptoms and prolong life rather than curing the disease.

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