Related Experiment Video
Updated: Apr 2, 2026
Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy
Published on: October 28, 2022
[Effects of caffeine citrate on myelin basic protein in neonatal rats with hypoxic-ischemic brain damage]
Fa-Lin Xu1, Hui-Qing Cheng, Cai-Hong Wang
1Department of Neonatology, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. xufalin72@126.com.
Insights
Caffeine citrate treatment improved white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD). This neuroprotective effect may involve down-regulating adenosine A1 receptor expression, aiding recovery from HIBD.
Area of Science:
- Neuroscience
- Neonatal Research
- Pharmacology
Background:
- Hypoxic-ischemic brain damage (HIBD) is a significant cause of neonatal neurological impairment.
- Cerebral white matter is particularly vulnerable to HIBD, leading to long-term deficits.
- Myelin basic protein (MBP) is a key marker of myelin integrity and white matter health.
Purpose of the Study:
- To investigate the therapeutic potential of caffeine citrate in mitigating HIBD-induced white matter damage in neonatal rats.
- To explore the underlying mechanism, specifically the role of adenosine receptors, in caffeine citrate's neuroprotective effects.
Main Methods:
- Neonatal rats underwent hypoxic-ischemic brain damage (HIBD) induction.
- Caffeine citrate was administered at specific time points post-HIBD.
- Myelin basic protein (MBP) expression was assessed via immunohistochemistry.
- Adenosine A1 and A2a receptor mRNA levels were quantified using real-time PCR.
Main Results:
- HIBD significantly reduced MBP expression in the cerebral white matter.
- Caffeine citrate treatment significantly increased MBP expression compared to the HIBD group.
- Adenosine A1 receptor mRNA expression was elevated in HIBD and reduced by caffeine citrate treatment.
Conclusions:
- Caffeine citrate demonstrates neuroprotective effects against HIBD-induced white matter injury in neonatal rats.
- The beneficial mechanism of caffeine citrate may involve the down-regulation of adenosine A1 receptor expression.
Objective:
To study the effects of caffeine citrate on myelin basic protein (MBP) expression in the cerebral white matter of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the related mechanism.
Methods:
Forty-eight seven-day-old Sprague-Dawley neonatal rats were randomly assigned to 3 groups: sham operation (n=16), HIBD (n=16) and HIBD+caffeine citrate (n=16). The rats in the HIBD and HIBD+caffeine citrate groups were subjected to left common carotid artery ligation, and then were exposed to 80 mL/L oxygen and 920 mL/L nitrogen for 2 hours to induce HIBD. The rats in the sham operation group were only subjected to a sham operation, without the left common carotid artery ligation or hypoxia exposure. Caffeine citrate (20 mg/kg) was injected intraperitoneally before hypoxia ischemia (HI) and immediately, 24 hours, 48 hours and 72 hours after HI. The other two groups were injected intraperitoneally with an equal volume of normal saline at the corresponding time points. On postnatal day 12, the expression of MBP in the left subcortical white matter was detected by immunohistochemistry, and the levels of adenosine A1 receptor mRNA and A2a receptor mRNA in the left brain were detected by real-time PCR.
Results:
The expression of MBP in the left subcortical white matter in the HIBD group was lower than in the sham operation group (P<0.05). The MBP expression in the HIBD+caffeine citrate group was significantly higher than in the HIBD group, but was still lower than the sham operation group (P<0.05). Real-time PCR showed that the adenosine A1 receptor mRNA expression was significantly higher in the HIBD group than in the sham operation group, and it was significantly lower in the HIBD+caffeine citrate group than in the HIBD group (P<0.05).
Conclusions:
Caffeine citrate can improve brain white matter damage following HIBD in neonatal rats and the protection mechanism might be related with the down-regulation of adenosine A1 receptor expression.
