Neuroprotective effects of scallop-derived plasmalogen in a mouse model of ischemic stroke

CT scan of a brain after an ischemic stroke.

Feng T, Hu X, Fukui Y, Tadokoro K, Bian Z, Morihara R, Yamashita T, and Abe K. (2021) Neuroprotective effects of scallop-derived plasmalogen in a mouse model of ischemic stroke. Brain Research

Ischemic stroke results from an obstruction in a vessel supplying blood to the brain, preventing the brain from receiving oxygen. Typically, there is a very small window of time in which a person must seek medical help to minimize as much brain damage as possible after an ischemic event. Depending on the region affected by the obstruction, an ischemic stroke can cause paralysis or numbness, confusion, vision issues, dystonia, alexia, and agnosia to name a few. Inflammation and oxidative stress can further disrupt the neurovascular unit, therefore plasmalogens have been suggested as a potential ischemic stroke treatment. Plasmalogens are a class of phospholipid that contains a vinyl-ether bond at sn-1, giving these lipids unique roles in cells in membrane composition, membrane fusion, and preventing oxidative stress. With previous work showing plasmalogen supplementation reduced neuroinflammation and β-amyloid accumulation, and improved cognition in Alzheimer disease patients, Feng et al were interested in investigating the effect of scallop-derived plasmalogen administration in a mouse model of ischemic stroke, with focus on its effects on behavior, oxidative stress, and inflammation.

The ischemic stroke model was produced through 60 minutes of transient middle cerebral artery occlusion (tMCAO). The goal was to determine the impact of pretreating animals for 14 days with plasmalogen (10 mg/kg/day) on functional outcomes five days after tMCAO. Researchers used the Bederson’s score to detect neurologic defects, while the corner test and rotarod test were used to analyze motor function. Bederson’s score was not different between the vehicle group and the plasmalogen treated group 5 days after tMCAO. In the corner test, mice were scored on which direction they turn when placed into a corner throughout 10 trials. If there are no unilateral abnormalities, the mouse should turn to either side equally. During this test ischemic mice were found to preferentially turn towards the non-injured side (~7 out of 10), but plasmalogen administration was able to significantly improve this (~5 out of 10), suggesting that the plasmalogen treatment reduced deficits caused by tMCAO. As well, latency in the rotarod test was significantly improved with plasmalogen administration.

To determine whether the plasmalogen treatment had an effect on oxidative stress, immunohistochemistry of the brain staining for a lipid peroxidation marker, 4-HNE (4-hydroxynonenal), and a nucleic acid peroxidation marker, 8-OHdG (8-hydroxydeoxyguanosine) were analyzed. Five days after tMCAO both markers were found in the peri-infarct fields, the area around the region of cell death, in the vehicle treated animals (~110 cells/0.5 mm^2 and ~80 cells/0.5 mm^2, respectively), but the plasmalogen supplemented group showed fewer 4-HNE and 8-OHdG positive cells (~90 cells/0.5 mm^2 and ~60 cells/0.5 mm^2, respectively), suggesting that the plasmalogen treatment reduced oxidative stress. Immunohistochemistry was also used to investigate neuroinflammatory markers such as the microglia marker Iba-1, pro-inflammatory cytokines IL-1β and TNF-α, and an anti-inflammatory cytokine IL-10 in the peri-infarct areas 5 days after tMCAO. The vehicle treated group had significantly higher number of cells per 0.5 mm^2 positive for Iba-1, IL-1β, and TNF-α compared to the group that was supplemented with plasmalogens (Iba-1: ~65 compared to ~45; IL-1β: ~75 compared to ~45; TNF-α: ~65 compared to ~40).

Feng et al wanted to determine if plasmalogen supplementation would be a suitable treatment option for protecting the brain from damage caused by an ischemic stroke. They found that compared to the vehicle treated group, the plasmalogen treatment recovered the unilateral abnormalities seen in the corner test and reduced motor function deficits through increased latency but showed no improvement in the Bederson’s score. As well, the plasmalogen treatment reduced markers for oxidative stress and neuroinflammation compared to the vehicle group. As oxidative stress and inflammation are processes known to also damage the neurovascular unit and further exacerbate the effects of ischemic stroke, a treatment that can mitigate this damage could be very beneficial. The present study investigated the effectiveness of a plasmalogen pre-treatment, suggesting that prophylactic use of a plasmalogen treatment may reduce the impairments seen in patient’s following a stroke. More work looking at the ability of plasmalogen supplementation to recover any damage from an ischemic event after it occurs would be very interesting and perhaps more clinically useful.