Brain research
-
The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system (RAS), is known to modulate waking and rapid eye movement (REM) sleep. REM sleep decreases between 10 and 30 days postnatally in the rat, with the majority occurring between 12 and 21 days. We investigated the possibility that changes in the cholinergic, muscarinic and/or nicotinic, input to PPN neurons could explain at least part of the developmental decrease in REM sleep. ⋯ The mixed muscarinic agonist carbachol (CAR) hyperpolarized all type II (A current) PPN cells and depolarized all type I (low threshold spike-LTS current) and type III (A+LTS current) PPN cells, but did not change effects during the period known for the developmental decrease in REM sleep. The effects of CAR persisted in the presence of TTX but were mostly blocked by the muscarinic antagonist atropine (ATR), and the remainder by MEC. We conclude that, while the nicotinic inputs to the PPN may help modulate the developmental decrease in REM sleep, the muscarinic inputs appear to modulate different types of cells differentially.
-
Mortality after serious systemic thermal injury may be linked to significant increases in cerebral vascular permeability and edema due to blood-brain barrier (BBB) breakdown. This BBB disruption is thought to be mediated by a family of proteolytic enzymes known as matrix metalloproteinases (MMPs). The gelatinases, MMP-2 and MMP-9, digest the endothelial basal lamina of the BBB, which is essential for maintaining BBB integrity. ⋯ MMP-9 protein levels and enzyme activity began to increase at 7 h and reached significant levels between 7 and 24 h after thermal injury. While MMP-9 protein levels continued to increase significantly through 72 h, enzyme activity returned to control level. The increase in MMP-9 expression and activity, associated with increased BBB permeability following thermal injury, indicates that MMP-9 may contribute to observed cerebral edema in peripheral thermal injury.
-
In the diseased central nervous system, astrogliosis is accompanied by microglial activation. Depending on the context of their activation, reactive astrocytes are involved in neuronal survival and regeneration in an either protective or impedimental way. Major reactive changes of astrocytes in vivo are the upregulation of the intermediate filaments GFAP (glial fibrillary acidic protein) and vimentin with accompanying cellular hypertrophy and/or hyperplasia. ⋯ Nevertheless, LPS-activated microglia stimulated astrocytes as demonstrated by an increased cell number and an enhanced mRNA expression of IL-6. Resting microglia did not change any of the determined parameters. Our results suggest that the role of activated microglia in astrogliotic processes following injury of the brain has to be reevaluated, as microglia in their activated state might support the onset of astrogliosis on the one hand, but might delay or reduce subsequent glial scar formation on the other hand.
-
The lingual nerve, a peripheral branch of the trigeminal nerve, can be damaged during the surgical removal of lower third molar teeth. This damage can lead to the development of dysaesthesia, with some patients complaining of burning pain. We investigated the hypothesis that vanilloid receptor 1 (TRPV1), a transducer of noxious heat stimuli, was involved in the development of this burning pain. ⋯ Furthermore, there was no correlation between TRPV1 expression and the VAS scores for pain, tingling or discomfort. However, if data from all patients was pooled, there was a negative correlation between the level of TRPV1 expression and the time after initial injury. These data do not rule out involvement of TRPV1 in the aetiology of burning dysaesthesia following lingual nerve injury but suggest that TRPV1 at the injury site does not play a primary role.
-
Hippocampal damage contributes to cognitive dysfunction after traumatic brain injury (TBI). We previously showed that Fluoro-Jade, a fluorescent stain that labels injured, degenerating brain neurons, quantifies the extent of hippocampal injury after experimental fluid percussion TBI in rats. Coincidentally, we observed that injured neurons in the rat hippocampus also stained with Newport Green, a fluorescent dye specific for free ionic zinc. ⋯ Treatment with lamotrigine, which inhibits presynaptic release of glutamate and presumably zinc that is co-localized with glutamate, reduced numbers of Fluoro-Jade-positive and Newport Green-positive neurons equally as did treatment with nicardipine, which blocks voltage-gated calcium channels through which zinc enters neurons. To confirm using molecular techniques that Fluoro-Jade and Newport Green-positive neurons are equivalent populations, we isolated total RNA from 25 Fluoro-Jade-positive and 25 Newport Green-positive pyramidal neurons obtained by laser capture microdissection (LCM) from the CA3 subfield, linearly amplified the mRNA and used quantitative ribonuclease protection analysis to demonstrate similar expression of mRNA for selected TBI-induced genes. Our data suggest that therapeutic interventions aimed at reducing neurotoxic zinc levels after TBI may reduce hippocampal neuronal injury.