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Effects of lateral fluid percussion injury on cholinergic markers in the newborn piglet brain
Cornelius K Donat1, Bernd Walter, Tanja Kayser
1Institute of Interdisciplinary Isotope Research, Leipzig, Germany. donat@iif-leipzig.de
Insights
Traumatic brain injury in piglets increased acetylcholine esterase activity in several brain regions early after injury. However, this injury did not cause loss of cholinergic neurons in the basal forebrain.
Area of Science:
- Neuroscience
- Pediatric Traumatology
- Neurochemistry
Background:
- Traumatic brain injury (TBI) is a significant cause of childhood death and disability.
- Adult animal models show TBI alters central cholinergic neurotransmission.
- The impact of TBI on cholinergic function in immature brains remains poorly understood.
Purpose of the Study:
- To investigate the effects of traumatic brain injury on cholinergic function in the immature brain.
- To test the hypothesis that TBI affects acetylcholine esterase activity and causes cholinergic neuron loss in developing brains.
Main Methods:
- Severe fluid percussion traumatic brain injury (FP-TBI) was induced in newborn piglets.
- Acetylcholine esterase histochemistry was performed on brain slices.
- Immunohistochemistry identified choline acetyltransferase and low-affinity neurotrophin receptor positive cells.
- Regional cerebral blood flow and brain oxygen availability were measured.
Main Results:
- Regional cerebral blood flow and brain oxygen availability decreased within 2 hours post-FP-TBI.
- Acetylcholine esterase activity significantly increased in the neocortex, basal forebrain, hypothalamus, and medulla.
- The number of cholinergic neurons in the basal forebrain remained unaffected by the injury.
Conclusions:
- Traumatic brain injury in immature brains leads to increased relative acetylcholine esterase activity early after injury.
- Despite increased enzyme activity, there was no observed loss of cholinergic neurons in the basal forebrain.
- These early neurochemical changes may contribute to developmental impairments following pediatric TBI.
Abstract:
Traumatic brain injury is a leading cause of death and disability in children. Studies using adult animal models showed alterations of the central cholinergic neurotransmission as a result of trauma. However, there is a lack of knowledge about consequences of brain trauma on cholinergic function in the immature brain. It is hypothesized that trauma affects the relative acetylcholine esterase activity and causes a loss of cholinergic neurons in the immature brain. Severe fluid percussion trauma (FP-TBI, 3.8+/-0.3atm) was induced in 15 female newborn piglets, monitored for 6h and compared with 12 control animals. The hemispheres ipsilateral to FP-TBI obtained from seven piglets were used for acetylcholine esterase histochemistry on frozen sagittal slices, while regional cerebral blood flow and oxygen availability was determined in the remaining eight FP-TBI animals. Post-fixed slices were immunohistochemically labelled for choline acetyltransferase as well as for low-affinity neurotrophin receptor in order to characterize cholinergic neurons in the basal forebrain. Regional cerebral blood flow and brain oxygen availability were reduced during the first 2h after FP-TBI (P<0.05). In addition, acetylcholine esterase activity was significantly increased in the neocortex, basal forebrain, hypothalamus and medulla after trauma (P<0.05), whereas the number of choline acetyltransferase and low-affinity neurotrophin receptor positive cells in the basal forebrain were unaffected by the injury. Thus, traumatic brain injury evoked an increased relative activity of the acetylcholine esterase in the immature brain early after injury, without loss of cholinergic neurons in the basal forebrain. These changes may contribute to developmental impairments after immature traumatic brain injury.
