Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease
Abstract Over a decade's experience of post‐stroke rehabilitation by administering the specific anti‐TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral lev...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
|
| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.1136 |
| _version_ | 1797658909393027072 |
|---|---|
| author | Ian A. Clark Bryce Vissel |
| author_facet | Ian A. Clark Bryce Vissel |
| author_sort | Ian A. Clark |
| collection | DOAJ |
| description | Abstract Over a decade's experience of post‐stroke rehabilitation by administering the specific anti‐TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post‐stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post‐chemotherapy, post‐irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non‐infectious origin, through reversing excess TNF generation by microglia. |
| first_indexed | 2024-03-11T18:06:13Z |
| format | Article |
| id | doaj.art-763eeb788d654238b279b83006fefdff |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-03-11T18:06:13Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-763eeb788d654238b279b83006fefdff2023-10-17T07:30:29ZengWileyPharmacology Research & Perspectives2052-17072023-10-01115n/an/a10.1002/prp2.1136Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological diseaseIan A. Clark0Bryce Vissel1Research School of Biology, Australian National University Canberra Australian Capital Territory AustraliaSt Vincent's Hospital Centre for Applied Medical Research St Vincent's Hospital Darlinghurst AustraliaAbstract Over a decade's experience of post‐stroke rehabilitation by administering the specific anti‐TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post‐stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post‐chemotherapy, post‐irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non‐infectious origin, through reversing excess TNF generation by microglia.https://doi.org/10.1002/prp2.1136activated microgliaautocrine feedback loopendometriosis painlong COVIDpost‐strokepsychiatric states |
| spellingShingle | Ian A. Clark Bryce Vissel Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease Pharmacology Research & Perspectives activated microglia autocrine feedback loop endometriosis pain long COVID post‐stroke psychiatric states |
| title | Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease |
| title_full | Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease |
| title_fullStr | Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease |
| title_full_unstemmed | Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease |
| title_short | Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease |
| title_sort | autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease |
| topic | activated microglia autocrine feedback loop endometriosis pain long COVID post‐stroke psychiatric states |
| url | https://doi.org/10.1002/prp2.1136 |
| work_keys_str_mv | AT ianaclark autocrinepositivefeedbackoftumornecrosisfactorfromactivatedmicrogliaproposedtobeofwidespreadrelevanceinchronicneurologicaldisease AT brycevissel autocrinepositivefeedbackoftumornecrosisfactorfromactivatedmicrogliaproposedtobeofwidespreadrelevanceinchronicneurologicaldisease |