The Contribution of Dysfunctional Chloride Channels to Neurovascular Deficiency and Neurodegeneration

Inhibition of Selective and Non-Selective Siclooxyigenase on Ansiolitic Effects Induced Diazepam in Mice

“…This is thought to occur because of an increase in arachidonic acid levels due to unchanging prostaglandins in which arachidonic acid can inhibit the transmission of GABA neurotransmitters which ultimately results in an excitation effect of. 4,6 In table 2. the results showed a decrease in the duration of open arms between the group given and the group given diazepam with ketoprofen or with celecoxib, where the highest percentage reduction was indicated by the group given diazepam with celecoxib; this could indicate that cox-2 selective inhibitors were given more influential in decreasing the anxiolytic effect of diazepam compared to non-selective, in contrast to a study conducted by Gambel which stated that the use of COX-2 inhibitors could be used to treat depression due to psychiatric problems by increasing the time in open arms.…”

Early Development of the GABAergic System and the Associated Risks of Neonatal Anesthesia

“…Examples of the excitatory system’s involvement include glutamatergic and astrocytic pathways which utilize nitric oxide (NO), calcium ions (Ca 2+ ), potassium ions (K + ), and arachidonic acid metabolites to help produce local increases in cerebral blood flow ([ 33 , 34 , 35 , 36 ]) (for a review of how these components contribute to the neurovascular coupling, see [ 37 ]). However, recent reviews [ 34 , 38 ] have indicated that these mechanisms may not completely account for all aspects of neurovascular coupling. The authors report caveats, such as: NO is not the active signaling molecule in the cerebral cortex (though its presence is necessary for vasodilation to occur), Ca 2+ increases from astrocyte projections are not necessary for vasodilation to occur and often take place following a significant latency period after the initiation of vasodilation and K + siphoning via astrocytes does not always play a major part in neurovascular coupling.…”

“…In addition to the increased metabolic rate in such a case, due to the elevated frequency of action potentials, GABAergic facilitation of the hemodynamic response would also become compromised. Combined, these effects, of an increase in oxygen demand and a weakened hemodynamic response, can lead to hypoxic conditions [ 38 ] which may participate in the long-term side effects of neonatal anesthesia.…”

“…However, elevated levels of neuronal apoptosis are still present in less severe but chronic cases of hypoxia [ 144 , 145 ]. For chronic hypoxia to manifest the brain tissue oxygen should reach a specific “threshold” level when the biochemical properties of brain tissue start to change [ 38 ]. The formation of ROS is a typical result of cell metabolism.…”

“…Since neurovascular deficiency develops much later after neonatal anesthesia exposure, it raises the question of how it can be entangled with neurodegenerative diseases. The GABAergic system typically operates through Cl − channels and, thus, it is important to acknowledge that there are several neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s and Huntington’s disease) which are associated with the dysfunction of these channels [ 38 ]. More specifically, selected studies have reported increased amyloid-β protein levels in response to neonatal anesthesia [ 154 , 155 , 156 ].…”