How does cerebrospinal fluid help to protect the central nervous system?

II Functions of Cerebrospinal Fluid

Cerebrospinal fluid has four major functions: (1) physical support of neural structures, (2) excretion and “sink” action, (3) intracerebral transport, and (4) control of the chemical environment of the central nervous system. Cerebrospinal fluid provides a “water jacket” of physical support and buoyancy. When suspended in CSF, a 1500-gm brain weighs only about 50 gm. The CSF is also protective because its volume changes reciprocally with changes in the volume of intracranial contents, particularly blood. Thus, the CSF protects the brain from changes in arterial and central venous pressure associated with posture, respiration, and exertion. Acute or chronic pathological changes in intracranial contents can also be accommodated, to a point, by changes in the CSF volume (Fishman, 1992; Milhorat, 1987; Rosenberg, 1990).

The direct transfer of brain metabolites into the CSF provides excretory function. This capacity is particularly important because the brain lacks a lymphatic system. The lymphatic function of the CSF is also manifested in the removal of large proteins and cells, such as bacteria or blood cells, by bulk CSF absorption (see Section II.D). The “sink” action of the CSF arises from the restricted access of water-soluble substances to the CSF and the low concentration of these solutes in the CSF. Therefore, solutes entering the brain, as well as those synthesized by the brain, diffuse freely from the brain interstitial fluid into the CSF. Removal may then occur by bulk CSF absorption or, in some cases, by transport across the choroid plexus into the capillaries (Davson and Segal, 1996; Fishman, 1992; Milhorat, 1987; Rosenberg, 1990).

Because CSF bathes and irrigates the brain, including those regions known to participate in endocrine functions, the suggestion has been made that CSF may serve as a vehicle for intracerebral transport of biologically active substances. For example, hormone releasing factors, formed in the hypothalamus and discharged into the CSF of the third ventricle, may be carried in the CSF to their effective sites in the median eminence. The CSF may also be the vehicle for intracerebral transport of opiates and other neuroactive substances (Davson and Segal, 1996; Fishman, 1992; Milhorat, 1987; Rosenberg, 1990).

An essential function of CSF is the provision and maintenance of an appropriate chemical environment for neural tissue. Anatomically, the interstitial fluid of the central nervous system and the CSF are in continuity (see Section II.A); therefore, the chemical composition of the CSF reflects and affects the cellular environment. The composition of the CSF (and the interstitial fluid) is controlled by cells forming the interfaces, or barriers, between the “body” and the neural tissue. These semipermeable interfaces, the blood-brain barrier, the blood-CSF barrier, and the CSF-brain barrier, control the production and absorption of CSF and provide a fluid environment that is relatively stable despite changes in the composition of blood (Davson and Segal, 1996; Fishman, 1992; Milhorat, 1987; Rosenberg, 1990).

Abstract

The cerebrospinal fluid (CSF) and interstitial fluids (ISF) are critical for preserving normal brain cell function. Choroid plexus epithelial cells and cerebral capillaries secrete the CSF/ISF, which acts as the lymph fluid of the brain. Normally about 500 mL of CSF is produced daily and an equal amount is absorbed across the arachnoid granulations. Failure to remove the CSF/ISF results in hydrocephalus if the ventricles are obstructed or increased intracranial pressure. Sampling the CSF by lumbar puncture is an essential clinical procedure in the diagnosis of brain infections and immunological diseases. Damage to the blood–brain barrier results in life-threatening brain edema.

ABNORMAL INFLAMMATORY CELLS

Inflammatory cells such as macrophages, plasma cells, and eosinophils are an abnormal finding in CSF. They may accompany malignancy, but are also seen in a variety of non-neoplastic conditions.

Macrophages have abundant, vacuolated cytoplasm that sometimes contains ingested cells, organisms, or pigment (Fig. 6.10).

Macrophages in cerebrospinal fluid are associated with:

meningitis

subarachnoid hemorrhage

intraventricular hemorrhage

cerebral infarction

post-treatment inflammation

multiple sclerosis36

Plasma cells are also an abnormal but nonspecific finding in CSF (Fig. 6.11).

Plasma cells in cerebrospinal fluid are associated with:

viral meningitis (e.g., enterovirus, human immunodeficiency virus [HIV])

Lyme disease

tuberculosis

cysticercosis

syphilis

multiple sclerosis36

Polymorphonuclear leukocytes are a normal finding if there is contamination by peripheral blood, but numerous neutrophils unaccompanied by a proportionate increase in red blood cells raise the possibility of acute meningitis (Fig. 6.12). In a patient with acquired immune deficiency syndrome (AIDS), numerous neutrophils are highly suggestive of cytomegalovirus (CMV) radiculopathy. Viral cytopathic inclusions, however, are not seen. The diagnosis of CMV radiculopathy can be confirmed by viral culture.37

DIFFERENTIAL DIAGNOSIS OF NEUTROPHILS IN CEREBROSPINAL FLUID:

peripheral blood contamination

acute bacterial meningitis

CMV radiculopathy

Toxoplasma meningoencephalitis

viral meningitis (early stage)

Eosinophils are rare in CSF; when present, especially in large numbers (Fig. 6.13), they suggest a parasitic infection, particularly Taenia solium and Angiostrongylus cantonensis.38

DIFFERENTIAL DIAGNOSIS OF EOSINOPHILS IN CEREBROSPINAL FLUID:

parasites

Coccidioides immitis

ventriculoperitoneal shunts

Rocky Mountain spotted fever

Formation, Flow, and Function of Cerebrospinal Fluid

CSF is an actively transported ultrafiltrate of plasma that bathes the CNS.1 The CSF is located in the ventricles of the brain and subarachnoid space of the spinal canal (Figure 10.2-1) and originates from the choroid plexus and ependymal lining of the ventricles.2 CSF flows from the ventricular system up over the cerebral hemispheres and through the subarachnoid space surrounding the spinal cord.1 Pulsation of blood in the choroid plexuses forces the CSF in a caudad direction. The rate of CSF production varies from 0.017 ml/min in cats to 0.5 ml/min in human beings3 and is independent of the blood hydrostatic pressure. The rate of CSF production for horses has not been determined. Osmotic and hypertonic solutions such as mannitol and dimethyl sulfoxide, when added to blood, decrease CSF production and decrease CSF pressure and edema.1

Collections of arachnoid villi (arachnoid granulations) are located in the venous sinus or the cerebral vein and absorb CSF. CSF absorption is related directly to the pressure gradient between the CSF and venous sinus. When CSF pressure exceeds venous pressure, these villi act as one-way ball valves forcing CSF flow to the venous sinus.4

CSF functions to suspend the brain and spinal cord for protection, regulate intracranial pressure, and maintain the proper ionic and acid-base balance.1

Cerebrospinal fluid analysis

Cerebrospinal fluid collection and analysis are indicated when plain radiographs do not provide a complete diagnosis. A lumbar puncture is recommended for CSF collection, and the needle may be left in place for myelography, pending the results of the cytologic examination of CSF. The alterations in CSF caused by spinal tumors should be interpreted according to the same criteria discussed for brain tumor diagnosis;76 however, it must be remembered that the protein content of CSF collected from a lumbar location is normally higher than that of CSF collected from the cerebellomedullary cistern.82 Lymphoma affecting the spinal cord often results in an elevated white cell count, predominantly abnormal lymphocytes.178,182

Biochemical Assays

Cerebrospinal fluid glucose, electrolyte, and enzyme (CK and LDH) concentrations are not routinely evaluated in ruminant medicine. Reported normal concentrations of glucose in the CSF are approximately 80% of the contemporary blood glucose concentrations. Decreases in CSF glucose concentrations have been associated with bacterial infections.12,21 Increased CK and LDH CSF concentrations have been associated with neurologic diseases.21,22 However, they provide little additional information in the establishment of a precise diagnosis.

In some cases of salt poisoning (hypernatremia) and hypomagnesemia, animals may present neurologic signs despite normal serum electrolyte values.1,2 In such cases, determination of Na and Mg CSF concentrations may help. Sodium CSF concentrations above 160 mEq/L or a CSF/serum-sodium ratio greater than 1 is diagnostic for salt poisoning.1 Likewise, a magnesium CSF concentration below 1.45 mg/dl is sufficient for diagnosis of hypomagnesemia.2 However, CSF is difficult to obtain on animals with clinical signs of hypomagnesemia.

Frequent Indications

CSF analysis requires general anesthesia. CSF is the only readily accessible tissue that evaluates current CNS status and is warranted every time a CNS disorder is suspected. Primary CNS inflammatory diseases rarely cause CBC or serum biochemical profile changes. If CBC or profile changes occur, a multisystemic disorder with secondary CNS involvement is likely. CSF analysis is indicated even if the CBC and profile are normal. Repeated CSF analysis can help evaluate response to treatment and obtain baseline data before discontinuation of treatment. It is good practice to routinely collect and analyze CSF obtained before conducting myelograms.

Cerebrospinal fluid copper

Cerebrospinal fluid (CSF) copper levels are elevated in persons with WD and neurological dysfunction and decline with successful symptomatic treatment (Weisner et al., 1987). Some investigators suggested that CSF copper levels may be the most accurate reflection of brain copper load (Hartard et al., 1993). In one report in which CSF copper concentrations were measured in four WD patients, the average treatment time to normalize CSF copper content (< 20 μg/L) was 47 months (Stuerenburg, 2000). Measurement of CSF copper is not performed in routine clinical practice and should be considered strictly a research tool.

Solute Removal from Cerebrospinal Fluid

That CSF volume and pressure remain constant over time reflects the equal rates at which CSF formation and removal occur. In the rat, this rate represents a complete turnover of the CSF volume (0.15 ml) every 1–2 hr, such that the half-life of most CSF solutes is ˜0.75 hr (9). Cerebrospinal fluid removal occurs via bulk flow, and solutes are generally cleared from CSF with the same rate constant regardless of size. Exceptions to this rule include certain neuropeptides and neurotransmitters, for which high-affinity receptors or enzymatic clearance mechanisms are present on the surface of the brain. In such cases, clearance from CSF may occur much more rapidly. Angiotensin II, for example, has a CSF half-life of <1 min, owing to enzymatic degradation (14).

Anti-CD20 (rituximab)

CSF B cells were not depleted in 4 subjects with PPMS treated with rituximab, a B-cell-depleting anti-CD20 monoclonal antibody (Monson et al., 2005). Rituximab did, however, temporarily suppress the activation state of B cells in CSF (Monson et al., 2005). In comparison, B lymphocytes were depleted in both the CSF and peripheral blood in a single subject with RRMS treated with rituximab (Stuve et al., 2005). In a study of 26 patients with MS who had CSF sampled before and after rituximab infusion, CSF B-cell levels were markedly decreased or undetectable in all subjects (Piccio et al., 2010). CSF T-cell levels were reduced in 21 subjects (81%) (Piccio et al., 2010). Post treatment with rituximab CSF CXCL13 and CCL19 levels decreased; the decline in CSF T-cell levels correlated with the decrease in CXCL13 levels (Piccio et al., 2010). The CSF IgG index and concentration and OCBs were unchanged following treatment (Piccio et al., 2010). Similar cellular findings were reported in a single case report (Petereit et al., 2008).