Palmitic acid methyl ester is a novel neuroprotective agent against cardiac arrest.

We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator first identified and released from the superior cervical ganglion and remain understudied. Thus, we investigated PAME's role in modulating cerebral blood flow (CBF) and neuroprotection after 6 min of cardiac arrest (model of global cerebral ischemia). Our results suggest that PAME can enhance CBF under normal physiological conditions, while administration of PAME (0.02 mg/kg) immediately after cardiopulmonary resuscitation can also enhance CBF in vivo. Additionally, functional learning and spatial memory assessments (via T-maze) 3 days after asphyxial cardiac arrest (ACA) suggest that PAME-treated rats have improved learning and memory recovery versus ACA alone. Furthermore, improved neuronal survival in the CA1 region of the hippocampus were observed in PAME-treated, ACA-induced rats. Altogether, our findings suggest that PAME can enhance CBF, alleviate neuronal cell death, and promote functional outcomes in the presence of ACA.

Utilizing the Modified T-Maze to Assess Functional Memory Outcomes After Cardiac Arrest.

BACKGROUND: Evaluating mild to moderate cognitive impairment in a global cerebral ischemia (i.e. cardiac arrest) model can be difficult due to poor locomotion after surgery. For example, rats who undergo surgical procedures and are subjected to the Morris water maze may not be able to swim, thus voiding the experiment. New Method: We established a modified behavioral spontaneous alternation T-maze test. The major advantage of the modified T-maze protocol is its relatively simple design that is powerful enough to assess functional learning/memory after ischemia. Additionally, the data analysis is simple and straightforward. We used the T-maze to determine the rats' learning/memory deficits both in the presence or absence of mild to moderate (6 min) asphyxial cardiac arrest (ACA). Rats have a natural tendency for exploration and will explore the alternate arms in the T-maze, whereas hippocampal-lesioned rats tend to adopt a side-preference resulting in decreased spontaneous alternation ratios, revealing the hippocampal-related functional learning/memory in the presence or absence of ACA. RESULTS: ACA groups have higher side-preference ratios and lower alternations as compared to control. Comparison with Existing Method(s): The Morris water and Barnes maze are more prominent for assessing learning/memory function. However, the Morris water maze is more stressful than other mazes. The Barnes maze is widely used to measure reference (long-term) memory, while ACA-induced neurocognitive deficits are more closely related to working (short-term) memory. CONCLUSIONS: We have developed a simple, yet effective strategy to delineate working (short-term) memory via the T-maze in our global cerebral ischemia model (ACA).

Interruption of perivascular sympathetic nerves of cerebral arteries offers neuroprotection against ischemia.

Sympathetic nervous system activity is increased after cardiopulmonary arrest, resulting in vasoconstrictor release from the perivascular sympathetic nerves of cerebral arteries. However, the pathophysiological function of the perivascular sympathetic nerves in the ischemic brain remains unclear. A rat model of global cerebral ischemia (asphyxial cardiac arrest, ACA) was used to investigate perivascular sympathetic nerves of cerebral arteries via bilateral decentralization (preganglionic lesion) of the superior cervical ganglion (SCG). Decentralization of the SCG 5 days before ACA alleviated hypoperfusion and afforded hippocampal neuroprotection and improved functional outcomes. These studies can provide further insights into the functional mechanism(s) of the sympathetic nervous system during ischemia. NEW & NOTEWORTHY: Interruption of the perivascular sympathetic nerves can alleviate CA-induced hypoperfusion and neuronal cell death in the CA1 region of the hippocampus to enhance functional learning and memory.