Microdialysis

Spinosin, a major bioactive herbal ingredient isolated from Semen Ziziphi Spinosae, plays an important role in sedation and hypnosis. However, the pharmacokinetic behavior of spinosin in special sites has not been reported. Microdialysis (MD) technique, as a continuous, realtime monitoring sampling technique, is very suitable for the evaluation of the disposition of diverse drugs.

PURPOSE: Because of the large and continuous energetic requirements of brain function, neurometabolic dysfunction is a key pathophysiologic aspect of the epileptic brain. Additionally, neurometabolic dysfunction has many self-propagating features that are typical of epileptogenic processes, that is, where each occurrence makes the likelihood of further mitochondrial and energetic injury more probable. Thus abnormal neurometabolism may be not only a chronic accompaniment of the epileptic brain, but also a direct contributor to epileptogenesis.

As the major inhibitory neurotransmitter in human brain, GABA is an important modulator of hyperexcitability in epilepsy patients. Given the high energetic cost of neurotransmission and synaptic activity, GABA concentrations may be hypothesized to correlate with metabolic function.

OBJECTIVES: The aim of this study was to examine the release of nitric oxide (NO) and cGMP in response to electroacupuncture (EA) stimulation in the acupuncture point (acupoint), compared to the non-meridian control area. METHODS: Thirty samples of dermal microdialysis data were collected from 24 volunteers at pericardium (PC) 4 and control area. EA was applied to PC 3 by using a 5-V pulse with a duration of 1.0 milliseconds at 10 Hz for 15 minutes. Dialysate samples were continuously collected 20 minutes each before, during, and after EA for two hours.

We studied the metabolic responses to different DA concentrations elicited by four doses of D-amphetamine (AMPH, 0, 0.25, 0.5, 1.0, or 3.0 mg/kg). We compared the degree of DA release (via microdialysis) with striatal cAMP activity and whole brain maps of cerebral blood volume (rCBV) changes (via pharmacological MRI, phMRI). RESULTS: AMPH increased DA release in the caudate/putamen (CPu) and cAMP activity in the CPu, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in a linear dose-dependent manner (P < 0.0001).

Middle cerebral artery occlusion (MCAO) is a popular model in experimental stroke research and causes prominent ischemic damage in the forebrain. To characterize metabolic changes induced by MCAO, we have induced permanent MCAO in mice that were implanted with a microdialysis probe in either striatum or hippocampus. Immediately after the onset of ischemia, glucose levels dropped to <10% of basal values in the striatum while they dropped to 50%, and recovered thereafter, in hippocampus.

Characterization of the ontogeny of the cerebral dopaminergic system is crucial for gaining a greater understanding of normal brain development and its alterations in response to drugs of abuse or conditions such as attention-deficit hyperactivity disorder. Pharmacological MRI (phMRI) was used to determine the response to dopamine transporter (DAT) blockers cocaine and methylphenidate (MPH), the dopamine releaser D-amphetamine (AMPH), the selective D1 agonist dihydrexidine, and the D2/D3 agonist quinpirole in young (<30 days old) and adult (>60 days old) rats.

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40-50% when given at 10mg/kg 1h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests.

PURPOSE: Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. METHODS: We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate.

A dynamic microdialysis sampling method with liquid chromatography-quadrupole time-of-flight mass spectrometry (Q-TOF-MS) was developed for rapid and sensitive analysis of the metabolite profile of Panax notoginseng extract (PNE) in rat bile. In vivo studies in male Sprague-Dawley rats were performed with microdialysis probes implanted into the bile duct before bile samples were collected from 0 to 12h. Metabolites of PNE were identified using dynamic adjustment of the fragmentor voltage to produce structure-relevant fragment ions.