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Dietary LPC-Bound n-3 LCPUFA Protects against Neonatal Brain Injury in Mice but Does Not Enhance Stem Cell Therapy
Eva C Hermans1, Carlon C E van Gerven1, Line Johnsen2
1Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, 3508 AB Utrecht, The Netherlands.
Insights
Oral Lysoveta, a lysophosphatidylcholine (LPC)-bound n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA), reduced brain injury in neonatal mice after hypoxic-ischemic (HI) events. However, it did not improve functional outcomes or enhance mesenchymal stem cell (MSC) therapy effectiveness.
Area of Science:
- Neuroscience
- Biochemistry
- Pediatrics
Background:
- Neonatal hypoxic-ischemic (HI) brain injury is a significant cause of neurological disability.
- n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) show promise in preclinical models.
- Lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs may improve brain incorporation, but their efficacy in HI is unknown.
Purpose of the Study:
- To evaluate the neuroprotective effects of oral LPC-n-3 LCPUFAs (Lysoveta) in a neonatal mouse model of HI.
- To investigate potential additive or synergistic effects of Lysoveta combined with MSC therapy.
- To explore the in vitro neuroprotective mechanisms of Lysoveta against oxidative stress.
Main Methods:
- Neonatal C57BL/6 mice underwent hypoxic-ischemic (HI) induction.
- Mice received oral Lysoveta for 7 days, with or without intranasal MSCs administered at 3 days post-HI.
- Functional outcomes were assessed using behavioral tests (cylinder rearing, novel object recognition, open field).
- Histological analysis evaluated gray matter (MAP2) and white matter (MBP) injury.
- In vitro studies assessed Lysoveta's protection of SH-SY5Y neurons against oxidative stress.
Main Results:
- Oral Lysoveta significantly reduced gray and white matter injury in HI mice.
- Lysoveta treatment did not improve functional deficits in behavioral tests.
- Combination therapy with Lysoveta and MSCs did not yield superior outcomes compared to MSCs alone.
- In vitro, Lysoveta demonstrated neuroprotection against oxidative stress in SH-SY5Y neurons.
Conclusions:
- Short-term oral administration of Lysoveta LPC-n-3 LCPUFAs offers neuroprotection against neonatal HI brain injury, primarily by mitigating oxidative stress.
- Lysoveta alone does not ameliorate functional deficits post-HI and does not enhance the therapeutic efficacy of MSCs.
- Further research is needed to optimize delivery and assess long-term effects and functional recovery.
Abstract:
Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21-28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.
