Background
Inflammation in the central nervous system
Cytokines
Interleukin-1β
Tumor necrosis factor-α
Interleukin-6
Prostaglandins
Platelet-activating factor
CD44
Matrix metalloproteinase-9
Toll-like receptors
Chemokines
Neurological disorders and epilepsy
Neurological disorders | Inflammatory contribution to epilepsy development |
---|---|
Traumatic brain injury | Damage associated molecular pattern (DAMP) stimulation of immune system Significant CCL2 increase Neutrophil recruitment —> BBB damage Reactive oxygen species (ROS) release —> activate vascular endothelium —> T cell infiltration of BBB [137] |
Status epilepticus | Elevated IL-1β, TNF-α, IL-6 transcript levels Albumin extravasation <—>BBB breakdown EP2-COX2 upregulation TLR pathways stimulated [138] |
Multiple sclerosis | Increased oxidative stress and ROS Activation of microglia Recruitment of T-cells, B-cells, and macrophages [139] |
GBM | IL-8 up-regulation via EGFRvIII IL-6-mediated STAT3 activation IL-1β-dependent activation of NF-κB, p38 MAPK and JNKs pathways [140] |
Stroke | TNF-α, IL-1Β, IL-6 upregulation ICAM and VCAM upregulation MMP-9 increase MCP-1,(MIP-1α), fractalkine (CX3CL1) increase [141] |
Alzheimer’s disease | MCP-1, cytokines (IL-6, TNF-α), CXCL8, CCL5 increase Deposition of Aβ generates ROS Activation of the complement cascade [142] |
Blood–brain barrier breakdown
Inflammatory mediators overview
Leukocyte adhesion and infiltration
Astrocyte reactivity
Systemic inflammation
Systemic inflammatory condition | Associated inflammatory findings | Odds ratio (compared to control group) | Prevalence of epilepsy | Incidence of epilepsy |
---|---|---|---|---|
Systemic lupus erythematous (SLE) | Antibodies: ANA, dsDNA, SS-A/SS-B.Upregulates anti- MAP-2 and anti NMDR presence in CSF IL-1β, Il-8, IFN gamma activate microglia. IL-10 upregulates spinogenesis | 7-fold [91] | 2.5% [91] Up to 8 times higher than non-SLE population | 2.86-fold greater than non-SLE cohort [96] |
Rheumatoid arthritis (RA) | Upregulated TNF-α,IL-1 and IL-6 cytokines | 3.5-fold [91] | 1.2% [91] | 1.27-fold greater than control cohort [130] |
Type I diabetes | Autoantibodies GAD 45 | 5.2-fold [91] | 1.8% [91] 2–3.7% [120] | 2.2-fold greater than control cohort [143] |
Celiac disease | Anti-endomysial antibodies (EMA), anti-tissue transglutaminase antibodies (tTG), and anti-gliadin antibodies (AGA) | 4.5-fold [91] | 1.5% [91] | – |
Sjogrens | Lymphocyte infiltration of CD4+ T cells, B cells, and plasma cells | 4.3-fold [91] | 1.5% [91] | |
Crohn’s Disease | Th1 and Th17 pathways CD44, IL-6, TNF-a upregulated | 3.1-fold [91] | 1.1% [91] 3.5–5.9% [105] | – |
Ulcerative Colitis | IL-5, IL-13, IL-15 with Th2 upregulation | 2.5 fold [91] | 0.9% [91] | – |
Hashimoto’s thyroiditis | Circulating immune complexes Anti-thyroid antibodies | 2.4-fold [91] | 0.8% [91] | – |
Behcet’s | HLA-B51 Neuronal lymphocytosis | – | – | |
Anti-phospholipid syndrome | Antibodies directed against membrane anionic phospholipids | – | – |