We demonstrate fluorescence-detected two-dimensional electronic spectroscopy (F-2DES) with a broadband, continuum probe pulse pair in the pump-probe geometry. The approach combines a pump pulse pair generated by an acousto-optic pulse-shaper with precise control of the relative pump pulse phase and time delay with a broadband, continuum probe pulse pair created using the Translating Wedge-based Identical pulses eNcoding System (TWINS). The continuum probe expands the spectral range of the detection axis and lengthens the waiting times that can be accessed in comparison to implementations of F-2DES using a single pulse-shaper. We employ phase-cycling of the pump pulse pair and take advantage of the separation of signals in the frequency domain to isolate rephasing and non-rephasing signals and optimize the signal-to-noise ratio. As proof of principle, we demonstrate broadband F-2DES on a laser dye and bacteriochlorophyll a.
Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anticonvulsants/pharmacology , Convulsants , Diclofenac/pharmacology , Epilepsy/chemically induced , Epilepsy/drug therapy , Levetiracetam/pharmacology , Pilocarpine , Animals , Behavior, Animal/drug effects , Drug Synergism , Epilepsy/mortality , Male , Mice , Seizures/chemically induced , Seizures/mortality , Seizures/prevention & control , Survival Analysis
We present a rapid-scanning approach to fluorescence-detected two-dimensional electronic spectroscopy that combines acousto-optic phase-modulation with digital lock-in detection. This approach shifts the signal detection window to suppress 1/f laser noise and enables interferometric tracking of the time delays to allow for correction of spectral phase distortions and accurate phasing of the data. This use of digital lock-in detection enables acquisition of linear and nonlinear signals of interest in a single measurement. We demonstrate the method on a laser dye, measuring the linear fluorescence excitation spectrum as well as rephasing, non-rephasing, and absorptive fluorescence-detected two-dimensional electronic spectra.
