High frequency of gastrointestinal yeast presence in ASD subjects was shown through a simple cultural approach (Candida spp. in 57.5 % of ASDs and no controls); the identification of aggressive form (pseudo-hyphae presenting) of Candida spp. at light microscope means that adhesion to intestinal mucosa is facilitated. Dysbiosis appears sustained by lowered Lactobacillus spp. and decreased number of Clostridium spp. Absence of C. difficilis and its toxins in both ASDs and controls is also shown. Low-mild gut inflammation and augmented intestinal permeability were demonstrated together with the presence of GI symptoms. Significant linear correlation was found between disease severity (CARs score) and calprotectin and Clostridium spp. presence. Also GI symptoms, such as constipation and alternating bowel, did correlate (multivariate analyses) with the increased permeability to lactulose. The present data provide rationale basis to a possible specific therapeutic intervention in restoring gut homeostasis in ASDs.
Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests, or activities. Strong inflammation states are associated with ASD. This inflammatory condition is often linked to immune system dysfunction. Several cell types are enrolled to trigger and sustain these processes. Neuro-inflammation and neuro-immune abnormalities have now been established in ASD as key factors in its development and maintenance. In this review, we will explore inflammatory conditions, dysfunctions in neuro-immune cross-talk, and immune system treatments in ASD management.
Background: Neuropathic pain (NP) is an incurable disease caused by a primary lesion in the nervous system. NP is a progressive nervous system disease that results from poorly defined neurophysiological and neurochemical changes. Its treatment is very difficult. Current available therapeutic drugs have a generalized nature, sometime acting only on the temporal pain properties rather than targeting the several mechanisms underlying the generation and propagation of pain. Methods: Using biomolecular and immunohistochemical methods, we investigated the effect of the systemic injection of human mesenchymal stem cells (hMSCs) on NP relief. We used the spared nerve injury (SNI) model of NP in the mouse. hMSCs were injected into the tail vein of the mouse. Stem cell injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored every 10 days starting from day 11 until 90 days after surgery. Results: hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once injected into the tail vein. An anti-nociceptive effect was detectable from day 11 post surgery (7 days post cell injection). hMSCs were mainly able to home in the spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1β and IL-17 and increased protein levels of the mouse anti-inflammatory interleukin IL-10, and the marker of alternatively activated macrophages CD106 in the spinal cord of SNI mice. Conclusion: As a potential mechanism of action of hMSCs in reducing pain, we suggest that they could exert their beneficial action through a restorative mechanism involving: (i) a cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible for switching pro-inflammatory macrophages to anti-inflammatory macrophages; (ii) secretion of a broad spectrum of molecules to communicate with other cell types. This study could provide novel findings in MSC pre-clinical biology and their therapeutic potential in regenerative medicine.
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