Abstract Considerable debate exists regarding the cellular source of prostaglandins in mammalian central nervous system (CNS). At least two forms prostaglandin endoperoxide synthase, or cyclooxygenase (COX), principal enzyme biosynthesis these mediators, are known to exist. Both have been identified CNS, but only distribution COX 1 has mapped detail. In this study, we used Western blot analysis and immunohistochemistry describe biochemical characterization anatomical second,...

1. Extracellular pH (pHo) was measured in the cerebellar cortex of rat using a recently developed liquid membrane ion-selective micropipette (ISM). pHo determined during stimulus-evoked neuronal activity, elevated extracellular potassium concentration, [K+]o, spreading depression (SD), and complete ischemia. In many experiments [K+]o simultaneously determined. 2. A train local surface stimuli (LOC) produced an initial alkaline shift from base line 7.20-7.30 to 7.25-7.35. This followed by...

Although commonly considered a disease of white matter, gray matter demyelination is increasingly recognized as an important component multiple sclerosis (MS) pathogenesis, particularly in the secondary progressive phase. Extent damage to strongly correlated decline memory and cognitive dysfunction MS patients. Aging likewise occurs with from myelin loss, age-associated failure remyelinate significantly contributes progression. However, recent evidence demonstrates that parabiotic exposure...

The effects of neocortical spreading depression (SD) on the expression immunoreactive c-fos protein were examined within superficial laminae trigeminal nucleus caudalis (TNC), a brainstem region processing nociceptive information. KCl was microinjected into left parietal cortex at 9 min intervals over 1 hr, and SD detected by shift in interstitial DC potential adjacent frontal cortex. stained cells lower upper cervical spinal cord counted both sides after tissues sectioned (50 microns)...

Elevation of brain glucose before the onset nearly complete ischemia leads to increased lactic acid within brain. When excessive, such acidosis may be a necessary factor for converting selective neuronal loss infarction from ischemia. To examine potential neurotoxicity excessive concentrations, we microinjected (0.5 μl/min) 150 m M sodium lactate solutions (adjusted 6.50–4.00 pH) 20 min into parietal cortex anesthetized rats. Interstitial pH (pH 0 ) was monitored with hydrogen ion–selective...

We examined the relationships between intracellular pH (pHi) and interstitial (pHe) in a rat model of focal ischemia. Interstitial was measured with pH-sensitive microelectrodes, average tissue [14C]dimethadione method rats subjected to occlusion right middle cerebral common carotid arteries (MCA-CCAO). In normal cortex, pHe pHi were 7.24 +/- 0.97 7.01 0.13 (means SD, n = 6), respectively. ischemic fell 6.43 0.13, whereas decreased only 6.86 0.11 (n 5) 1 h after MCA-CCAO. After 4 ischemia,...

Intracellular pH (pHi) is an important physiologic variable that both reflects and influences cell function. Glial cells are known to alter their functional state in response a variety of stimuli accordingly may be expected display corresponding shifts pHi. We used fine-tipped, double-barreled, pH-sensitive microelectrodes continuously monitor pHi glial vivo from rat frontal cortex. Cells were identified as glia by high membrane potential lack injury discharge or synaptic potentials....

Reactive astrocytosis is a process by which astrocytes respond to brain injury showing an increase in glial fibrillary acidic protein (GFAP) staining that associated with hypertrophy and/or hyperplasia of these cells. Because spreading depression (SD) perturbation uncomplicated neuronal necrosis and seen both vivo vitro neural structures, we sought determine whether SD was sufficient stimulus induce enhanced GFAP staining. elicited anesthetized rats application KCI parietal cortex for 3 hr;...

Nearly complete brain ischemia under normoglycemic conditions results in death of only selectively vulnerable neurons. With prior elevation glucose, such injury is enhanced to include pancellular necrosis (i.e., infarction), perhaps because an associated, severe lactic acidosis preferentially injures astrocytes. However, no direct physiologic measurements exist support this hypothesis. Therefore, we used microelectrodes measure intracellular pH and passive electrical properties cortical...

Abstract : Prostaglandins (PGs) are potent modulators of brain function under normal and pathological conditions. The diverse effects PGs due to the various actions specific receptor subtypes for these prostanoids. Recent work has shown that PGE 2 , while generally considered a proinflammatory molecule, reduces microglial activation thus an antiinflammatory effect on cells. To gain further insight mechanisms by which influences microglia, we investigated subtype, i.e., EP1, EP2, EP3, EP4,...

Cerebral lactic acid, a product of ischemic anaerobic glycolysis, may directly contribute to brain damage in vivo. In this study we evaluated the effects extracellular acid exposure on 7-day-old cultures embryonic rat forebrain. Mixed neuronal and glial were exposed either or hydrochloric compare toxicities relatively permeable impermeable acids. Neurons resistant HCl acidosis, often surviving 10-min exposures pH 3.8. same cultures, immunochemically defined astrocytes survived maximum...

Modulation of intracellular pH is widely implicated in the control cell growth and metabolism, yet little known about brain function. To determine how stimulation may affect mammalian glial cells, rat cortical astrocytes were studied for first time vivo using pH-sensitive electrodes submicron caliber. Stimulation surface caused a cytoplasmic alkaline shift tenths within seconds. Cessation induced electrical activity was followed by recovery small acid rebound. Recordings obtained during...

Simultaneous measurements of tissue PCO2 (PtCO2), interstitial H+ concentration ([H+]o), and lactate content were used to examine changes in HCO3- ([HCO3-]o) during complete ischemia. In normoglycemic rats (blood glucose 6-8 mM; neocortical ischemic-induced 8-12 mmol/kg) [H+]o increased from 7.22 +/- 0.02 6.79 pH (n = 3). By contrast, hyperglycemic 18-75 19-31 rose by a significantly larger amount 6.19 7). Given that is the predominant buffer, peak PtCO2 show why bimodally distributed...

Spreading depression (SD), the most likely cause of migraine aura and perhaps migraine, occurs with increased oxidative stress (OS). SD increases reactive oxygen species (ROS), ROS, in turn, can signal to increase neuronal excitability,which includes susceptibility. also elevates tumor necrosis factor-α (TNF-α), which excitability. Accordingly, we probed for cellular origin OS from its relationship TNF-α, might promote SD, using rat hippocampal slice cultures. We observed significantly...

Microglia play an important role in fine‐tuning neuronal activity. In part, this involves their production of tumor necrosis factor‐alpha (TNFα), which increases excitability. Excessive synaptic activity is necessary to initiate spreading depression (SD). Increased microglial proinflammatory cytokines promotes initiation SD, which, when recurrent, may a conversion episodic high frequency and chronic migraine. Previous work shows that potentiation SD occurs through increased TNFα reactive...

Although intercellular Ca 2+ waves resemble spreading depression (SD) and occur in hippocampal organ cultures (HOTCs), SD has not been reported these cultures. Accordingly, electrophysiological imaging techniques were used to examine potential interrelations between changes of SD. Our results show, for the first time, that HOTCs can support Furthermore, two distinct found precede The traveled >100 μm/sec along pyramidal cell dendritic layer. second subsequently mostly perpendicular layer...

Spreading depression (SD) is thought to cause migraine aura, and perhaps migraine, includes a transient loss of synaptic activity preceded followed by increased neuronal excitability. Activated microglia influence play an important role in homeostatic scaling via release cytokines. Furthermore, enhanced function activates not only secrete cytokines but also increase the motility their branches, with somata remaining stationary. While SD increases from microglia, effects on microglial...

We have previously shown that CdSe/ZnS core/shell luminescent semiconductor nanocrystals or QDs (quantum dots) coated with PEG [poly(ethylene glycol)]-appended DHLA (dihydrolipoic acid) can bind AcWG(Pal)VKIKKP(9)GGH(6) (Palm1) through the histidine residues. The coating on QD provides colloidal stability and this peptide complex uniquely allows to be taken up by cultured cells readily exit endosome into soma. now show use of a polyampholyte [in which neutral is replaced negatively...

Eclampsia is defined in the obstetrical literature as occurrence of unexplained seizure during pregnancy a woman with preeclampsia. In Western world, incidence eclampsia ~1 per 2000 to 1 3000 pregnancies, but 10-fold higher tertiary referral centers and undeveloped countries where there poor prenatal care, multi-fetal gestations. Nearly 50 women die do 14 their offspring, mortality rates are considerably countries. also associated significant life-threatening complications, including...