Central Nervous System (CNS)

In the Spinal Cord, each segment is connected to a pair of spinal nerves. Each spinal nerve is joined to its segment of cord by a number of roots or rootlets grouped as dorsal (posterior) roots and ventral (anterior) roots. In a transverse section, there is partial division into left and right halves by the dorsal (posterior) median septum and the ventral (anterior) median fissure. The butterfly-shaped inner substance is called the gray matter. The white matter surrounds the gray matter.

• Gray matter surrounds the central canal and contains neurons, central neuroglia, and neuropil (tangled masses of nerve fibers and neuroglial cell processes around neurons).
• White matter is peripheral, containing mainly myelinated fibers. It originates from cell bodies lying either in gray matter of the spinal cord, brain, or spinal ganglia. It does not contain any cell bodies of neurons. It is divided into longitudinal columns (funiculi), including two dorsal funiculus, two lateral funiculus, and two ventral funiculus. It contains mainly ascending and descending myelinated axons, central neuroglia, and no perikarya or synapses. Myelin appears black when fixed specifically. Axons originate from neurons lying either in gray matter of the spinal code, brain, or dorsal root ganglia.

Thoracolumnar region (T1-L2) has small lateral horns. This is the site of motor neurons of the sympathetic division of the autonomic nervous system.

• Motor neurons are multipolar and have cell bodies in the ventral (anterior) horn of the gray matter (aka ventral horn neurons). They are very large, efferent neurons with a larger nucleus+nucleolus and cytoplasm rich in Nissl bodies. AXons of motor neurons leave the cord, passing through the ventral (anterior) root and becomes a part of the spinal nerve of that segment.
• Sensory neurons have cell bodies in the dorsal (posterior) root ganglia and cranial ganglia. Sensory neurons are afferent and pseudounipolar, i.e. have a single process that divides into a peripheral segment (receives info from the periphery) and a central segment (delivers info from the cell body to gray matter of the spinal cord or brain).

In the Brain:

• Gray matter forms the cortex, containing nerve cell bodies, axons, dendrites, glial cells, blood vessels, and sites of synapses.
• White matter forms the medulla, containing only myelinated axons of nerve cells, glial cells, and blood vessels.

Neurons of the cerebrum gray matter are arranged into SIX layers of neurons. Each layer houses neurons with a particular characteristic. H&E staining does not demonstrate the architecture of the gray matter. The cerebral cortex, part of the outer cerebrum, can be divided into three layers:

• Outer molecular layer
• Single layer of Purkinje cells, located between the outer molecular layer and inner granular layer. Contains numerous apical dendrites that arborize in the molecular layer. Purkinje cells have a single axon (not visible in H&E) that extends into the granular layer and represents beginning of outflow from the cerebrum.
• Inner molecular layer

There are three sequential CNS connective tissue membranes (aka the meninges, which cover the brain and spinal cord):

• Dura mater, which is the outermost layer that is continuous with the periosteum of the skull. It is a thick sheet of dense connective tissue. There are spaces within it lined with endothelium. It serves as the principal channel for blood returning from the brain.
• Arachnoid, which is beneath the dura. It is a delicate sheet of connective tissue loosely joined to the inner surface of the dura. It has delicate trabeculae attached to the pia surace. The space bridged by these trabeculae is called the subarachnoid space, which is filled with CSF.
• Pia mater, which is a delicate connective tissue layer resting directly on the surface of the brain and spinal cord. It is continuous with the perivascular connective sheath of the blood vessels of the brain and spinal cord.

The Blood-Brain Barrier (BBB) segregates the neurons of the CNS from the blood-borne molecules that can act as neurotransmitters. It provides protection against harmful substances (i.e toxic drugs, bacterial toxins, etc.). This is accomplished by tight junctions between endothelial cells of the capillaries (the morphological bases of the BBB). Substances must pass through (not between) the endothelial cells. Notably, few endocytotic vesicles are seen in brain endothelium (i.e. restriction of transendothelial transport). There is a relatively thick basement membrane around the capillaries. The BBB is maintained by astrocyte feet.

Response to Injury is a complex sequence of two events:

• Degeneration. In the PNS breakdown and phagocytosis of myelin sheath is done by Schwann cells and resident phagocytes. The nerve-blood barrier is disrupted along the entire length of the damaged axon. Massive recruitment of monocyte-derived macrophages speeds up myelin removal. Schwanna cells stop forming new myelin and start to divide by arranging themselves in lines along their external laminae. This arrangement is similar to the formation of long tubes with empty lumen. In the CNS oligodendrocytes undergo apoptosis when the axon is injured. The BBB is disrupted only at the site of injury and not along the entire length of the injured axon. This limits the infiltration of the monocyte-derived macrophage. Myelin removal takes months or even years, which is a major factor in the failure of nerve regeneration in the CNS. Glial (astrocyte-derived) scar replaces the empty spaces left by degenerated axons.
• Regeneration. Tubes collapse due to removal of myelin and axonal debris. Axons of the PNS regenerate rapidly, while axons of the CNS cannot regenerate. There is an inability of oligodendrocytes and microglia to phagocytose myelin debris, and the BBB restricts macrophage migration. Schwann cells are arranged in bands. Many new nerve cell processes (neurites or sprouts) regenerate from the end of the injured axon. After crossing the site of injury, only neurites that associate with cellular bands survive. Bands guide newly formed neurites to their destination (skeletal muscle). Neurites who fail to associate with bands will degenerate. Schwann cells around regenerated axon differentiate and make myelin sheath.