Automated Algorithm for Detection of Transient Adenosine Release

Borman, Ryan; Wang, Ying; Nguyen, Michael; Ganesana, Mallikarjunarao; Lee, Scott T.; Venton, B. Jill

doi:10.1021/acschemneuro.6b00262

Cited by 25 publications

(38 citation statements)

References 29 publications

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“…A training set was created for each animal using the seven largest transients in the pre-drug data [ 34 ]. For some of the data, an automated analysis program was used that identifies random adenosine transients from FSCV data sets [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Early changes in transient adenosine during cerebral ischemia and reperfusion injury

Ganesana

Venton

2018

PLoS ONE

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Adenosine is an important neuromodulator in the central nervous system, and tissue adenosine levels increase during ischemic events, attenuating excitotoxic neuronal injury. Recently, our lab developed an electrochemical fast-scan cyclic voltammetry (FSCV) method that identified rapid, spontaneous changes in adenosine concentrations that last only about 3 seconds. Here, we investigated the effects of cerebral ischemia and reperfusion on the concentration and frequency of transient adenosine release in the caudate-putamen. In anesthetized rats, data were collected for four hours: two hours of normoxia, 30 min of cerebral ischemia induced by bilateral common carotid artery occlusion, and 90 min of reperfusion. Transient adenosine release was increased during the cerebral ischemia period and remained elevated during reperfusion. The total number of adenosine transients increased by 52% during cerebral ischemia and reperfusion compared to normoxia. The concentration of adenosine per event did not increase but the cumulative adenosine concentration during cerebral ischemia and reperfusion increased by 53% because of the higher frequency of events. Further, we evaluated the role of A2A antagonist, SCH442416, a putative neuroprotective agent to affect adenosine transients. SCH442416 significantly decreased the transient frequency during cerebral ischemia-reperfusion by 27% and the cumulative concentration by 31%. Our results demonstrate that this mode of rapid adenosine release increases during early cerebral ischemia-reperfusion injury. Rapid adenosine release could provide fast, local neuromodulation and neuroprotection during cerebral ischemia.

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Section: Methodsmentioning

confidence: 99%

Early changes in transient adenosine during cerebral ischemia and reperfusion injury

Ganesana

Venton

2018

PLoS ONE

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“…Transients collected for TTX experiments were analyzed using a new automated algorithm and compared with control slices analyzed in the same manner. 52 All statistics were performed using Graphpad Prism 6. Mean values are given ± standard error of the mean (SEM).…”

Section: Methodsmentioning

confidence: 99%

Regional Variations of Spontaneous, Transient Adenosine Release in Brain Slices

Lee

Venton

2017

ACS Chem. Neurosci.

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Transient adenosine signaling has been recently discovered in vivo, where the concentration is on average 180 nM and the duration only 3-4 s. In order to rapidly screen different brain regions and mechanisms of formation and regulation, here we develop a rat brain slice model to study adenosine transients. The frequency, concentration, and duration of transient adenosine events were compared in the prefrontal cortex (PFC), hippocampus (CA1), and thalamus. Adenosine transients in the PFC were similar to those in vivo, with a concentration of 160 ± 10 nM, and occurred frequently, averaging one every 50 ± 5 s. In the thalamus, transients were infrequent, occurring every 280 ± 40 s, and lower concentration (110 ± 10 nM), but lasted twice as long as in the PFC. In the hippocampus, adenosine transients were less frequent than those in the PFC, occurring every 79 ± 7 s, but the average concentration (240 ± 20 nM) was significantly higher. Adenosine transients are largely maintained after applying 200 nM tetrodotoxin, implying they are not activity dependent. The response to adenosine A antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) differed by region; DPCPX had no significant effects in the PFC, but increased the average transient concentration in the thalamus and both the transient frequency and concentration in the hippocampus. Thus, the amount of adenosine available to activate receptors, and the ability to upregulate adenosine signaling with DPCPX, varies by brain region. This is an important consideration for designing treatments that modulate adenosine in order to cause neuroprotective effects.

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“…The Venton group recently published the first steps toward an automated data analysis algorithm for FSCV. 114 This approach assesses FSCV data for chemical information by first choosing a time to describe the background. After background subtraction, the algorithm identifies fluctuations in the concentration of the chosen analyte from the background-subtracted data.…”

Section: Fscv: Under Construction…mentioning

confidence: 99%