13 research outputs found
Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation
Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin
Spatial and seasonal variability of polygonal tundra water balance: Lena River Delta, northern Siberia (Russia)
The summer water balance of a typical Siberian
polygonal tundra catchment is investigated in order to
identify the spatial and temporal dynamics of its main
hydrological processes. The results show that, besides
precipitation and evapotranspiration, lateral flow considerably
influences the site-specific hydrological conditions.
The prominent microtopography of the polygonal tundra
strongly controls lateral flow and storage behaviour of the
investigated catchment. Intact rims of low-centred polygons
build hydrological barriers, which release storage
water later in summer than polygons with degraded rims
and troughs above degraded ice wedges. The barrier
function of rims is strongly controlled by soil thaw, which
opens new subsurface flow paths and increases subsurface
hydrological connectivity. Therefore, soil thaw dynamics
determine the magnitude and timing of subsurface outflow
and the redistribution of storage within the catchment.
Hydraulic conductivities in the elevated polygonal rims
sharply decrease with the transition from organic to
mineral layers. This interface causes a rapid shallow
subsurface drainage of rainwater towards the depressed
polygon centres and troughs. The re-release of storage
water from the centres through deeper and less conductive
layers helps maintain a high water table in the surface
drainage network of troughs throughout the summer