New research changes map of the lymphatic system and, possibly, treatment of neurological diseases

The stunning results of a research study conducted by the University of Virginia (UVA) School of Medicine, which were released in June of 2015, determined that the brain is directly connected to the immune system by vessels previously thought not to exist, contradicting previously long-held beliefs, especially considering how extensively the lymphatic system has been mapped throughout the body. Researchers at UVA believe that the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer’s disease to multiple sclerosis.

According to Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA’s Center for Brain Immunology and Glia (BIG,) “Instead of asking, ‘How do we study the immune response of the brain?’ ‘Why do multiple sclerosis patients have the immune attacks?’ now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels. It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.”

“I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” Dr. Kipnis stated. “I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.”

According to the article “Missing link found between brain, immune system — with profound disease implications,” released by the University of Virginia Health System, the discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis’ lab. The vessels were detected after Louveau developed a method to mount a mouse’s meninges – the membranes covering the brain – on a single slide so that they could be examined as a whole. The discovery means many new angles to explore when researching neurological disease.

In this video, Dr. Kipnis and Dr. Louveau discuss the research project and it’s surprising results:
 

The study raises some startling implications in regards to neurological disorders, such as Alzheimer’s Disease. “In Alzheimer’s, there are accumulations of big protein chunks in the brain. We think they may be accumulating in the brain because they’re not being efficiently removed by these vessels,” Kipnis said. “And there’s an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.”

For more information about the study, read the complete UVA Health Services article, “Missing link found between brain, immune system — with profound disease implications.”

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Additional Research Related to Autism

In addition to the UVA study, a number of other research projects pertaining to the neurological aspects of autism have been conducted in recent years, including:

• Mast cell activation and autism (Theoharis C. Theoharidesa, Asimenia Angelidoua, Konstantinos-Dionysios Alysandratosa, Bodi Zhanga, Shahrzad Asadia, Konstantinos Francisf, Elena Toniatog, Dimitrios Kalogeromitrose): Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social interactions, repetitive and stereotypic behaviors, as well as learning and sensory deficits. Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment. Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins.
  Download PDF of the study: Brain Mast Cells, Eur J Pharmacol July 2015
• Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders (Theoharis C. Theoharidesa, Marianna Athanassioua, Smaro Panagiotidoua, Robert Doyle): Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with Rett syndrome also have behavioral symptoms consistent with those of autism spectrum disorders (ASDs).
  Download PDF of the study: Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders
• Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism (Irene Tsilioni, Nicholas Dodman, A I Petra, A Taliou, Konstantinos Francis, Alice A Moon-Fanelli): Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by defects in communication and social interactions, as well as stereotypic behaviors. Symptoms typically worsen with anxiety and stress. ASD occur in early childhood, often present with regression and have a prevalence of 1 out of 68 children. The lack of distinct pathogenesis or any objective biomarkers or reliable animal models hampers our understanding and treatment of ASD.
  Download PDF of the study: Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism
• Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6 (I Tsilioni, A Taliou, K Francis, TC Theoharides1): Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interactions and communication, as well as stereotypic behaviors. As many as 50% of children with ASDs regress at 2–3 years old implying the involvement of some epigenetic triggers, such as high fever, infection, trauma, environmental toxins or stress. In spite of the identification of a number of mutations in children with ASDs, its pathogenesis remains unknown. Moreover there are no objective biomarkers for either diagnosis or prognosis making effective drug development difficult.
  Download PDF of the study: Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6

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