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Therapeutic effect of caffeine treatment immediately following neonatal hypoxic-ischemic injury on spatial memory in male rats.

Alexander M, Smith AL, Rosenkrantz TS, Fitch RH - Brain Sci (2013)

Bottom Line: The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes.We also found a reduction in right cortical volume (ipsilateral to injury) in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate.These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Connecticut, Storrs, CT 06269, USA. michelle.alexander@uconn.edu.

ABSTRACT
Hypoxia Ischemia (HI) refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P) 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen). Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p.) injection of caffeine (10 mg/kg), or vehicle (sterile saline) immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM) from P90 to P95. Results show that HI injured animals (with no caffeine treatment) displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury) in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

No MeSH data available.


Related in: MedlinePlus

(a–c) Total latencies (in seconds) across 4 trials/day are shown. (a) A significant difference between HI saline and sham was seen [F(1,21) = 3.274, p < 0.05, one tailed], with HI saline performing significantly worse than shams. (b) A significant difference between HI saline and HI caffeine treated animals was seen [F(1,28) = 8.477, p < 0.01], with HI saline animals performing significantly worse than HI caffeine. (c) No significant differences in treatment were seen between HI caffeine and sham animals [F(1,21) = 0.363, p > 0.05]. For all graphs, error bars represent standard error.
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brainsci-03-00177-f001: (a–c) Total latencies (in seconds) across 4 trials/day are shown. (a) A significant difference between HI saline and sham was seen [F(1,21) = 3.274, p < 0.05, one tailed], with HI saline performing significantly worse than shams. (b) A significant difference between HI saline and HI caffeine treated animals was seen [F(1,28) = 8.477, p < 0.01], with HI saline animals performing significantly worse than HI caffeine. (c) No significant differences in treatment were seen between HI caffeine and sham animals [F(1,21) = 0.363, p > 0.05]. For all graphs, error bars represent standard error.

Mentions: A 5 (Day) x 2 (Treatment) repeated measures ANOVA revealed a significant Treatment difference between HI saline and sham treated animals [F(1,21) = 3.274, p < 0.05, one-tailed], with the HI saline group taking longer to reach the platform than shams (Figure 1a). A further 5 (Day) x 2 (Treatment) repeated measures ANOVA also revealed a significant Treatment difference between HI saline and HI caffeine treated animals [F(1,28) = 8.477, p < 0.01], with the HI saline group taking longer to reach the platform compared to the HI caffeine group (Figure 1b). Finally a 5 (Day) x 2 (Treatment) repeated measures ANOVA revealed no significant differences between HI caffeine and sham animals [F(1,21) = 0.363, p > 0.05] (Figure 1c). The within variable Day showed a trend for the HI saline and sham comparison [F(4,84) = 1.599, p = 0.09, one tailed], but was significant for the HI saline vs. HI caffeine comparison [F(4,112) = 2.7, p < 0.05] as well as for the HI caffeine and sham comparison [F(4,84) = 2.824, p < 0.05]. As above, these Day effects reflect learning.


Therapeutic effect of caffeine treatment immediately following neonatal hypoxic-ischemic injury on spatial memory in male rats.

Alexander M, Smith AL, Rosenkrantz TS, Fitch RH - Brain Sci (2013)

(a–c) Total latencies (in seconds) across 4 trials/day are shown. (a) A significant difference between HI saline and sham was seen [F(1,21) = 3.274, p < 0.05, one tailed], with HI saline performing significantly worse than shams. (b) A significant difference between HI saline and HI caffeine treated animals was seen [F(1,28) = 8.477, p < 0.01], with HI saline animals performing significantly worse than HI caffeine. (c) No significant differences in treatment were seen between HI caffeine and sham animals [F(1,21) = 0.363, p > 0.05]. For all graphs, error bars represent standard error.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061822&req=5

brainsci-03-00177-f001: (a–c) Total latencies (in seconds) across 4 trials/day are shown. (a) A significant difference between HI saline and sham was seen [F(1,21) = 3.274, p < 0.05, one tailed], with HI saline performing significantly worse than shams. (b) A significant difference between HI saline and HI caffeine treated animals was seen [F(1,28) = 8.477, p < 0.01], with HI saline animals performing significantly worse than HI caffeine. (c) No significant differences in treatment were seen between HI caffeine and sham animals [F(1,21) = 0.363, p > 0.05]. For all graphs, error bars represent standard error.
Mentions: A 5 (Day) x 2 (Treatment) repeated measures ANOVA revealed a significant Treatment difference between HI saline and sham treated animals [F(1,21) = 3.274, p < 0.05, one-tailed], with the HI saline group taking longer to reach the platform than shams (Figure 1a). A further 5 (Day) x 2 (Treatment) repeated measures ANOVA also revealed a significant Treatment difference between HI saline and HI caffeine treated animals [F(1,28) = 8.477, p < 0.01], with the HI saline group taking longer to reach the platform compared to the HI caffeine group (Figure 1b). Finally a 5 (Day) x 2 (Treatment) repeated measures ANOVA revealed no significant differences between HI caffeine and sham animals [F(1,21) = 0.363, p > 0.05] (Figure 1c). The within variable Day showed a trend for the HI saline and sham comparison [F(4,84) = 1.599, p = 0.09, one tailed], but was significant for the HI saline vs. HI caffeine comparison [F(4,112) = 2.7, p < 0.05] as well as for the HI caffeine and sham comparison [F(4,84) = 2.824, p < 0.05]. As above, these Day effects reflect learning.

Bottom Line: The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes.We also found a reduction in right cortical volume (ipsilateral to injury) in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate.These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Connecticut, Storrs, CT 06269, USA. michelle.alexander@uconn.edu.

ABSTRACT
Hypoxia Ischemia (HI) refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P) 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen). Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p.) injection of caffeine (10 mg/kg), or vehicle (sterile saline) immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM) from P90 to P95. Results show that HI injured animals (with no caffeine treatment) displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury) in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

No MeSH data available.


Related in: MedlinePlus