The multisensory regulation of unconventional T cell homeostasis.

Unconventional T cells typically group γδ T cells, invariant Natural Killer T cells (NKT) and Mucosal Associated Invariant T (MAIT) cells. With their pre-activated status and biased tropism for non-lymphoid organs, they provide a rapid (innate-like) and efficient first line of defense against pathogens at strategical barrier sites, while they can also trigger chronic inflammation, and unexpectedly contribute to steady state physiology. Thus, a tight control of their homeostasis is critical to maintain tissue integrity. In this review, we discuss the recent advances of our understanding of the factors, from neuroimmune to inflammatory regulators, shaping the size and functional properties of unconventional T cell subsets in non-lymphoid organs. We present a general overview of the mechanisms common to these populations, while also acknowledging specific aspects of their diversity. We mainly focus on their maintenance at steady state and upon inflammation, highlighting some key unresolved issues and raising upcoming technical, fundamental and translational challenges.

Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus.

BACKGROUND: Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we determined the efficacy and mode of action of AZE in the rat . METHODS: We employed in vivo approaches including ICP and cerebrospinal fluid secretion measurements in anaesthetized rats and telemetric monitoring of ICP and blood pressure in awake rats in combination with ex vivo choroidal radioisotope flux assays and transcriptomic analysis. RESULTS: AZE effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect appeared to occur via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day. CONCLUSIONS: AZE lowers ICP directly via its ability to reduce the choroid plexus CSF secretion, irrespective of mode of drug administration.

Dataset on inflammation induced after lumbar puncture.

Neuroinflammation is evident and one of the primary induced responses after central nervous system (CNS) injury, lumbar puncture and CNS surgery. In rare cases, complications could arise after the lumbar puncture or CNS surgery leading to inflammation, bleeding or other problems such as cerebrospinal fluid (CSF) leakage. The present dataset describes the occurrence of such a condition after the dura breakage or postoperative complication leading to the development of neuroinflammation in the adult Wistar rats. Therefore, objective of the study is to report such a rare condition and detect the most reliable glial proteins upregulated 2-3 weeks after the lumbar puncture which may help the neuroscience community to a better understanding their cause of action. In response to neuroinflammation, glial cells leak into the extracellular space, where they can be identified in the CSF or serum and may act as diagnostic biomarkers. Laminectomy was performed at the thoraco-lumbar (T12-L1) region and the dura was punctured. After that, the exposed part was covered with silica gel and adhesive followed by dental cement. The skin was closed using sterile sutures. After, the rats were given buprenorphine (0.05 mg/kg, every 8 h for 3 days) and carprofen (5 mg/kg, once a day for 5 days) as analgesic and anti-inflammatory and baytril (5 mg/kg, once a day for 10 days) as antibiotic drugs. Note, the buprenorphine and lidocaine were also given before starting the procedure. After the laminectomy, the functional outcomes of the rats were tested (starting from the day of surgery to the last day) and the rats which were locomoting normally using all the limbs were included in the study. In case of any decompression, the functional outcomes showing any kind of laming or partial paralysis of hindlimbs were excluded from the study. Unexpected neuroinflammation has occurred 2-3 weeks after performing the given procedure. Data presented in the article implicate active microglia measured by using protein biomarker such as Iba-1 [1, 3] and astrocytes measured by using Glial fibrillary acidic protein (GFAP) [2, 3] and S100 (strongly targets S100B and weakly A1) [7, 8] in the CSF collected two-three weeks after the laminectomy and dura breakage from the adult rats. Later paraformaldehyde (PFA) fixed spinal cord slices were also collected from the animals and immunolabelled with the same biomarkers. Western blots were performed with the collected CSF which showed high expression of glial markers such as GFAP, Iba-1 and S100 which has shown to target S100B with no expression of A1 (or A2, play an important role in neuroprotection) astrocytes which have recently been shown to be produced by microglia at the site of injury [9]. However, S100B [10] and GFAP [2] are known to be adequately discharged by the distinct cells in stress conditions which seems to occur in the present report. In addition, the spinal slices immunolabelled with the same biomarkers also showed increased expression of glia. Cross-talk between microglia-astrocyte in CNS stress is crucial for the neurons to survive and function after the injury. Reactive microglia (shown by high Iba-1 expression) leading to microgliosis comprise the first line of defense to phagocytose the dead cells [11]. Astrocytes act as the second line of defense leading to a process known as astrogliosis and upregulate GFAP and S100B to limit the damage [12]. Further studies are needed to explain the molecular mechanism/s of different astrocytes release such as A2 and their interaction with microglia after the lumbar puncture.