II.4.2) INFLAMMATORY RESPONSE
The lack of host defenses in the CSF allows rapid
multiplication of bacterial pathogens resulting in the release of microbial
products such as lipopolysaccharide[36]. The hall mark of bacterial meningitis
is recruitments of neutrophils into the cerebo spinal fluid(Figure 4)[37].
Neutrophil extravasation to any site of inflammation depends on the coordinated
sequential expression at the cell surface of specific adhesion molecule,
notably L-selectin (CD62l) is expressed at the cell surface and allows the
neutrophil to «roll» along the endothelium.For extravasation to
proceed L-selectin must be removed from the surface of neutrophil and
expression of the B2 integrin CD11b /CD18 must be upregulated[36].
Neutrophil adherence to endothelium occurs through the
interaction of neutrophil CD11b/CD18 and diapedesis and migration of neutrophil
along a chemotactic gradient to focus of inflammation that follows. The removal
of L-selectin and integrin upregulation are achieved by neutrophil activation
which occurs when the cell encounters activated endothelium (IL-8 and PAF are
typical activators of endothelium)[36].
II.4.3) RAISED INTRACRANIAL PRESSURE
Intracranial pressure often rises in meningitis and can lead
to life threatening cerebral herniation. Three pathophysiologic mechanisms
contribute to the development of cerebral oedema[37]. They are;Vasogenic,
Cytotoxic and Interstitialoedema. Vasogenicoedema occurs directly as a result
of the increased permeability of the blood brain barrier[37]. Cytotoxic oedema
is the rise in intracellular water due to loss of cellular homeostatic
mechanism and cell membranes function, attributed to the release of toxins from
neutrophil or organisms. Anti-diuretic hormone (ADH) release leads to
hypotonicity of cerebral extracellular fluid and increase the permeability of
the brain to water. Interstitial oedema is the result of an imbalance between
cerebo spinal production and resorption, and occurs when blood flow or cerebo
spinal resorption is impaired[37].
15
Figure 4 : Pathogenesis of bacterial meningitis
[38]
II.4.4) NEURONAL DAMAGE
Bacterial meninges causes disabling neuropsychological
deficits in up to 50 % of its survivors with the hippocampus most affected and
vulnerable area of the brain. The extracellular fluid around the brain cell is
contiguous with the cerebo spinal fluid and the proximity to the ventricular
system allows diffusion between those compartments around could deliver soluble
bacterial and inflammatory toxic mediators[37].
16
Neuronal damage in meninges involve bacterial toxins,
cytotoxic products of immune competent cells and indirect pathology secondary
to intracranial complications(Figure 4)[38]. In the case of Streptococcus
pneumoniae is associated with the highest frequency of neuronal damage, produce
two major toxins identified; H2O2 and Pneumolysin a pore forming cytolysin[37].
They cause programmed death of neurons and microglia by inducing rapid
mitochondrial damage. Pneumolysin translocate to mitochondria and induce pore
formation in mitochondrial membranes. Release of apoptosis inducing factor
(AIF) from damaged mitochondria leads to fragmentation of DNA and apoptosis
like cell death[37]. The cell death is executed in the Caspase-independent
manner, where cells exposed to live Pneumolysin cannot be rescued by caspase
inhibitors but somehow any intervention from those inhibitors, z-VAD-fmk there
is a 50% chance to avoid neuronal damage[37].
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