PMC full text:
Front Cell Neurosci. 2015; 9: 519.
Published online 2016 Jan 19. doi: 10.3389/fncel.2015.00519
Table 1
Evidence of neuroinflammation/encephalitis in the brains and cerebral spinal fluid (CSF) of subjects with autism spectrum disorder (ASD).
| Studies | N Case/Control | Findings | Researchers’ Conclusion |
|---|---|---|---|
| Vargas et al., 2005 | 15/12 | (1) Marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues | Active neuroinflammatory process in those with an ASD diagnosis |
| 6/9 | (2) CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1 | ||
| Li et al., 2009 | 8/8 | Proinflammatory cytokines (TNF-alpha, IL-6, and GM-CSF), Th1 cytokine (IFN-gamma) and chemokine (IL-8) were significantly increased in the brains of ASD patients compared with the controls | Brain inflammation in those with an ASD diagnosis and autoimmune disorder |
| Young et al., 2011 | 9/9 | Neurons, astrocytes, and microglia all demonstrated increased extranuclear and nuclear translocated NF-κB p65 expression in brain tissue from ASD donors relative to samples from matched controls | Part of a putative molecular cascade leading to brain inflammation |
| Morgan et al., 2010 | 13/9 | Microglial activation and increased microglial density in the dorsolateral prefrontal cortex in those with autism | Neuropathological alteration and brain inflammation |
| Morgan et al., 2012 | 13/9 | Microglia are more frequently present near neurons in the autism cases at a distance interval of 25 μm, as well as 75 and 100 μm | Aberrantly close microglia-neuron association in the ASD disorder |
| Wei et al., 2011 | 6/6 | Interleukin (IL)-6 increased in the cerebellum of autistic subjects | Localized inflammation of the central nervous system |
| Tetreault et al., 2012 | 11/12 | Individuals with autism had significantly more microglia compared to controls in the fronto-insular and visual cortex | The brain’s immune cells (microglia) are probably denser throughout cerebral cortex in ASD |
| Suzuki et al., 2013 | 20/20 | Excessive microglial activation in multiple brain regions in young adult subjects with an ASD diagnosis was found using regional brain [11C](R)-PK11195 binding potential as a representative measure of microglial activation | Augmented but not altered microglial activation (brain immune-cell activation), which is indicative of pro-inflammatory processes in the brain |
| Fatemi et al., 2008 | 24/22 | The levels of recognized indicators of inflammatory processes in brain tissue, including Aquaporin 4 and Connexin 43 were examined in the brains of those with an autism diagnosis. The study found that, in contract to controls, in evaluations using the brain’s β-actin level as a reference, Aquaporin 4 expression was decreased significantly in cerebellum, while, in Brodmann’s area 9 (superior frontal cortex), Connexin 43 was elevated in the brains of those diagnosed with autism. | Inflammatory processes in ASD |
| Chez et al., 2007 | 10 | Elevation of cerebrospinal fluid levels of TNF-α was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) | Indicative of CNS inflammatory mechanisms |
| Laurence and Fatemi, 2005 | 3 | Elevated levels of GFAP in the frontal, parietal, and cerebellar cortices using age-matched autism and control post-mortem brain specimens | Indicative of microglial and astroglial activation |
| Increased GFAP levels signify gliosis, reactive injury in those with an ASD diagnosis | |||
| Rosengren et al., 1992 | 47/13 | GFAP levels in CSF in children with autism were higher than those in normal control children | Indicate reactive astrogliosis in the CNS |
| Ahlsen et al., 1993 | 47/25 | Average levels of GFAP in the CSF of children with autism three times higher than control group | Reactive gliosis |
| Bailey et al., 1998 | 6/8 | Cerebellum in autism showed an increase in GFAP | Reactive gliosis |
| López-Hurtado and Prieto, 2008 | 8/7 | The mean density of glial cells was greater in the autistic cohort than controls in area 22 (p < 0.001), area 39 (p < 0.01), and area 44 (p < 0.05) | Results are consistent with accelerated neuronal death in association with gliosis and lipofuscin accumulation |
| Rose et al., 2012 | 12/12 | 3-chlorotyrosine (3-CT; an established biomarker of a chronic inflammatory response) significantly increased in autism cerebellum and BA22 | Chronic inflammatory response |
| Crawford et al., 2015 | 14/14 | Levels of GFAP immunoreactivity were significantly elevated (P = 0.008) in anterior cingulate cortex (Brodmann area 24; BA24) white matter of ASD compared to controls | Activation of white matter astrocytes in the anterior cingulate cortex as a result of a yet undefined cellular insult |