Effects of hyperoxia and therapeutic hypothermia in an immature rat model of neonatal hypoxicischaemic brain damage

• Main Author: Smit, Elisa
• Published: University of Bristol 2015
• Subjects: 618.92
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.685357

The introduction of therapeutic hypothermia and the guidance on the cautious use of oxygen during resuscitation of newborn infants are two of the greatest advances in neonatal care over the last decade. The combination of the two has not been researched in great detail, but is of great clinical relevance. This thesis discusses and investigates the use of 100% oxygen following resuscitation in an immature rat model of hypoxiaischaemia in combination with therapeutic hypothermia. Pups on postnatal day 7 are traditionally used in this model. However, pups on postnatal day 10 (P10) are more appropriate as a model for term hypoxicischaemic brain damage and this was developed as a new model. An increase in survival with mild brain injury was seen when using 100% oxygen during resuscitation in P10 pups. This will need to be further explored in larger animal models. An improved cerebral cortical blood flux was seen in pups resuscitated in 100% oxygen, which could be an explanation for the reduction in injury seen in survivors. No change in brain injury was seen following resuscitation in 100% oxygen in a model of severe hypoxia-ischaemia. An attempt was made to create a reproducible and more immature rat model for preterm hypoxia-ischaemia using pups on postnatal day 4. This was however difficult and the process is described. Add-on treatments to cooling are the future for infants with hypoxic-ischaemic encephalopathy and some of these will certainly be introduced as standard care in the coming decade. Further research investigating the side-effects of cooling and redefinition of the treatment (time-window, degree of hypothermia, patient selection) as well as investigating the combination of oxygen, therapeutic hypothermia and some of the new add-on treatments is highly desirable and suggested as a new avenue for exploration.