What Effector Cells Release in the CNS

1. T Cells (CD4+ and CD8+)

• IL-17 - drives neutrophil recruitment, disrupts blood-brain barrier
• IL-22 - inflammatory, barrier disruption

• Perforin - forms pores in target cell membranes
• Granzymes (A and B) - serine proteases that trigger apoptosis in target cells (neurons, oligodendrocytes)
• IFN-γ - antiviral and pro-inflammatory

Key textbook quote: "Activated T cells and the microglia-macrophages can contribute to tissue injury via non-antigen-restricted mechanisms. Each of these cell types releases an array of soluble factors... Cytokines characteristic of T cells include interleukin 2 (IL-2), interferon gamma (IFN-γ), and tumor necrosis factor β (TNF-β; lymphotoxin)."

• Bradley and Daroff's Neurology in Clinical Practice

2. Microglia / Macrophages (Resident + Recruited)

3. Astrocytes (Reactive Astrogliosis)

• IL-6, IL-1β - amplify inflammatory signals
• Chemokines (CXCL10, CCL2) - recruit T cells and monocytes into CNS
• Glutamate (excess) - excitotoxicity and neuronal death
• VEGF - promotes vascular permeability

4. NK Cells

• Perforin + Granzymes - kill infected or stressed neurons
• IFN-γ - activates macrophages and microglia
• TNF-α - cytotoxic effects

Summary Table

Preganglionic Sympathetic Outflow - Detailed

(Guyton & Hall - Red lines = preganglionic fibers; Black lines = postganglionic fibers)

1. Origin - Cell Bodies

• Located in the intermediolateral cell column (IML) / lateral horn of the spinal cord gray matter
• Spans segments T1 to L2 (some texts say T1-L3)
• This is why the sympathetic system is called the thoracolumbar outflow
• White rami communicantes exist only at T1-L2 levels

2. Fiber Characteristics

3. Path from Spinal Cord to Ganglion

1. Cell body in IML of lateral horn (T1-L2)
2. Axon exits via the ventral (anterior) root
3. Travels briefly in the spinal nerve
4. Diverges into the white ramus communicans (myelinated, so white)
5. Enters the paravertebral sympathetic chain ganglion

4. Three Fates After Entering the Sympathetic Chain

"After entering a paravertebral ganglion, a preganglionic sympathetic axon may (1) synapse within that segmental paravertebral ganglion, (2) travel up or down the sympathetic chain to synapse within a neighboring paravertebral ganglion, or (3) pass through the chain and then through one of the sympathetic nerves radiating outward from the chain, finally synapsing in a peripheral sympathetic (prevertebral) ganglion."

• Medical Physiology (Boron & Boulpaep)

5. Segmental Distribution of Preganglionic Outflow

The distribution is partly determined by the embryological origin of the organ. For example, the heart receives fibers from the neck region of the sympathetic chain because the heart originally developed in the neck of the embryo before descending into the thorax.

• Guyton & Hall Textbook of Medical Physiology

6. Ganglia Where Preganglionic Fibers Synapse

A. Paravertebral (Sympathetic Chain) Ganglia

• 22-23 ganglia arranged bilaterally along the vertebral column from cervical to coccyx
• Key named ganglia:

B. Prevertebral (Collateral) Ganglia

• Lie anterior to the aorta, near the roots of major visceral arteries
• Preganglionic fibers reach them via splanchnic nerves (bypass the chain without synapsing):

7. Special Case: Adrenal Medulla

• Preganglionic fibers from T5-T11 travel via greater splanchnic nerves all the way to the adrenal medulla without synapsing
• The chromaffin cells of the adrenal medulla are modified postganglionic neurons (embryologically derived from neural crest)
• These cells secrete epinephrine (80%) and norepinephrine (20%) directly into the bloodstream in response to ACh from preganglionic fibers
• This is why the adrenal medulla acts like a "sympathetic ganglion released into the blood"

"Preganglionic sympathetic nerve fibers pass without synapsing, all the way from the intermediolateral horn cells, through the sympathetic chains, through the splanchnic nerves, into the adrenal medullae. These secretory cells embryologically are derived from nervous tissue and are actually postganglionic neurons."

• Guyton & Hall

8. White vs. Gray Rami Communicantes

Summary Flowchart

IML lateral horn (T1-L2)
       ↓
Ventral root → Spinal nerve → White ramus communicans
       ↓
Sympathetic chain ganglion
  ├─ Synapse here → postganglionic via gray ramus → body wall, skin, blood vessels, sweat glands
  ├─ Ascend/Descend chain → synapse in cervical/lumbar ganglia → head, neck, legs
  └─ Pass through (no synapse) → splanchnic nerves → prevertebral ganglia → abdominal/pelvic viscera
                                                   ↓ (special)
                                           Adrenal medulla → epinephrine/norepinephrine released

Sympathetic Trunks - Brief

(Gray's Anatomy - Cervical sympathetic trunk with its three ganglia)

Overview

"On each side, a paravertebral sympathetic trunk extends from the base of the skull to the inferior end of the vertebral column where the two trunks converge anteriorly to the coccyx at the ganglion impar."

• Gray's Anatomy for Students

Structure

Regional Parts and Their Ganglia

1. Cervical Sympathetic Trunk

• No white rami here (no direct preganglionic input from the cord at cervical levels)
• Receives ascending preganglionic fibers from upper thoracic cord (T1-T3)
• Has 3 ganglia:

The stellate ganglion (cervicothoracic ganglion) is clinically important - blockade here causes Horner's syndrome (ptosis, miosis, anhidrosis, enophthalmos).

2. Thoracic Sympathetic Trunk

• ~12 ganglia (1st thoracic usually fused into stellate ganglion)
• Has both white and gray rami communicantes at each level
• Position: anterior to necks of ribs superiorly, shifting to costovertebral joints in mid-thorax, then anterolateral to vertebral bodies inferiorly
• Key contribution: gives rise to the splanchnic nerves (preganglionic fibers bypass the chain without synapsing here):

• Also contributes postganglionic fibers to the cardiac plexus, pulmonary plexus, aortic plexus, esophageal plexus

3. Lumbar Sympathetic Trunk

• ~4 ganglia
• Has white rami only from L1-L2 (end of thoracolumbar outflow)
• Gray rami to all lumbar spinal nerves
• Gives lumbar splanchnic nerves → inferior mesenteric ganglion and hypogastric plexus
• Lies on the anterolateral surface of lumbar vertebral bodies, medial to psoas major

4. Sacral Sympathetic Trunk

• ~4-5 ganglia on the anterior surface of the sacrum, medial to the anterior sacral foramina
• No white rami at sacral levels (no preganglionic input directly here)
• Gray rami to all sacral spinal nerves
• Contributes to the hypogastric plexus and innervation of pelvic organs

5. Ganglion Impar (Coccygeal Ganglion)

• Single unpaired ganglion where the two trunks merge in front of the coccyx
• The terminal point of the entire sympathetic chain

Rami Communicantes - Summary

Four Pathways for Preganglionic Fibers Once in the Trunk

1. Synapse in the ganglion at the same level they entered
2. Ascend or descend the trunk and synapse in a ganglion at a different level
3. Pass through the trunk and exit as splanchnic nerves to synapse in prevertebral ganglia
4. Pass through without synapsing to reach the adrenal medulla directly

Clinical Relevance