###### Abstract  
Under the optimal ultrasonification extraction conditions of 20.52 kHz for the frequency, 32.59 \({}^{\circ}\)C for the temperature, and 4.91 h for the process time, 17.98 mg/g of chlorophyll a was obtained. It was much higher than 13.81 mg/g from conventional 70% ethanol extraction and even higher than other data from _Spirulina_. This yield was close to the predicted value of 18.21 mg/g from the second-order polynomial model with a regression coefficient of 0.969. This model showed the greatest significance with the ultrasonic frequency and process time and the least significance with the temperature. The extracts also showed high \(\alpha\),\(\alpha\)-diphenyl-\(\beta\)-picrylhydrazyl (DPPH) radical scavenging activities as 69.38%, compared to 58.25% for the extracts from the 70% ethanol extraction. It was first shown that the optimal extraction was effective at enhancing the neuroprotective activities possibly due to the synergistic effects of higher amounts of chlorophyll a and other bioactive substances in the extract, revealing a 90% protection of the growth of mouse neuronal cells and a great reduction in Reactive Oxygen Species (ROS) production. Spirulina maxima; chlorophyll a; optimization; neuroprotective activities 1  
[PERSON], [PERSON], [PERSON], H.  
very high and has sharply increased compared to other chlorophylls such as chlorophyll b and c, etc. Therefore, _Spirulina_ is an economical bioresource of good-quality natural chlorophyll a since most of the chlorophylls in _Spirulina_ exist in the form of chlorophyll a, unlike most plants that have mixtures of chlorophyll a and b [11; 12]. However, the chlorophylls are very unstable and difficult to extract in intact forms out of the hard cells of _Spirulina_, which leads to very low extraction yields [13]. So far, the studies on chlorophyll extraction from _Spirulina_ have focused mainly on extracting the chlorophylls through the supercritical extraction process with different combinations of various parameters such as solvent ratio, temperature, pressure, etc. There were also several reports on obtaining fair amounts of chlorophylls from plant resources by optimizing those variables [14; 15]. However, most of the optimal conditions were at relatively high temperatures of 60-80 \({}^{\circ}\)C, which would cause a severe reduction in efficacy due to low contents of intact chlorophylls in the extracts. In addition to these difficulties, most extraction solvents, such as acetone, methanol, ether, etc., of the optimized extraction processes in the reports are not edible but were used since they are proven to be more efficient in extracting the chlorophylls than ethanol. However, the use of those inedible solvents would also cause a restriction in applications for the food industry [16]. Ultrasonic extraction has most often been used to break down cell walls with high efficiency, but without additional heat that could deteriorate heat-labile bioactive substances in the biomass [7; 17; 18; 19] because a high frequency of ultrasonic vibration with high power input will make many cavitation bubbles in an extraction solvent, and the shock waves and liquid jets generated by breaking the bubbles near the cell walls could effectively destruct hard cell membranes in a shorter time [19; 20]. However, there are still several hurdles to employing ultrasonic extraction processes in industrial applications such as relatively large equipment and more process controls as well as the difficulties of continuously combining with other processes such as fermentation and heating processes, etc. [21]. Therefore, in this work, a more realistic extraction process that uses ethanol, an edible solvent, will be optimized at a relatively low temperature by employing a simple ultrasonification process, not combined with other processes, which will minimally break down the structure and efficacy of the chlorophylll.