Acta Neurochir (Wien) (2002) 144: 195–200 Acta Neurochirurgica > Springer-Verlag 2002 Printed in Austria History of Neurosurgery Influence of Aging on Blood-Brain Barrier Permeability and Free Radical Formation Following Experimental Brain Cold Injury P. Erdinc ¸ler1, S. Tu ¨zgen1,U ¨ . D. Erdinc ¸ler2, E. Og ˇuz1, A. Korpınar3, N. C ¸ ıplak1, and C. Kuday1 1 Department of Neurosurgery, Cerrahpas ¸a Medical Faculty, Istanbul University, Turkey 2 Department of Geriatric Medicine, Cerrahpas ¸a Medical Faculty, Istanbul University, Turkey 3 Department of Biophysic, Cerrahpas ¸a Medical Faculty, Istanbul University, Turkey Summary The aim of this study is to investigate the e¤ects of experimental cold brain injury on blood-brain barrier integrity, on brain oedema formation, and on lipid peroxidation and to compare the results be- tween the aged and young rats. Cold brain injury was used to create a standard model of brain trauma in old and young rats. Disruption of the blood-brain barrier was analyzed by Evans blue method. The values of cerebral water content were calculated by using the fresh and dry weights of the cerebral hemispheres. Lipid peroxidation was assessed by measuring the tissue content of malonyl dialdehyde. Blood-brain barrier was destroyed significantly in young and old rats, but it was more severe in old rats. Accordingly, cerebral water content was increased in both groups, however this increase was sig- nificantly more prominent in old rats. No significant di¤erence was found on malonyl dialdehyde levels between young and old rats. The blood-brain barrier was more easily disrupted in old rats, and this was supposed to be the basic event causing more secondary damage. Keywords: Aging; brain oedema; blood-brain barrier; cold injury; lipid peroxidation. Introduction Compared with their younger counterparts, elderly patients are thought to have lower resistance to central nervous system (CNS) insults. This idea is certainly prevalent in the literature on head injury; however, the pathogenesis is not well understood [1, 8, 9, 16]. It has been frequently stated that the increased mortality rate in older brain-injured patients is a result of more fre- quent systemic complications [4, 13]. But, Baxt and Moody [3] have clearly demonstrated that, for multi- ple-injured patients, the severity of brain injury is the major determinant of mortality. The unfavorable out- come in elderly patients seems to be based upon an alteration in the pathophysiological response of the aging CNS to severe trauma, rather than on an in- creased incidence of age-related non-neurological com- plications [25]. The adverse e¤ect of age in cerebral injury is not restricted to trauma, but also holds true for ischaemia and subarachnoid haemorrhage [27]. The cardinal e¤ects of any insults to the CNS is the disruption of blood-brain barrier (BBB) integrity and resulting brain oedema accompanied by secondary damage which is mainly caused by free radicals. The aim of this study was to investigate the e¤ects of cold brain injury on BBB integrity, on brain oedema formation, and on lipid peroxidation in the brain of young and old rats. Materials and Methods Forty-seven 3 month old and forty-seven 36 month old male Wis- tar albino rats, bred at Istanbul University Centre for Experimental Medical Research and Application (DETAM), were used in the study. DETAM maintains a barrier-bred colony of rats of di¤erent ages of Wistar albino strain. In the life span of the Wistar albino rat, a 3 month old rat represents a fully mature, young adult, and a 36-month-old rat represents an elderly animal (i.e., approximately a 70-year-old human). Young rats weighed between 200–230 g and aged ones weighed between 400–420 g. The rats were divided into 10 groups (Table 1) – 4 control and 6 trauma – and anaesthetized with intraperitoneal ketamine (50 mg/kg). All animals were free to access water and food before and after the experiments. Craniectomy and Performance of Cold Injury This stage of procedure was accomplished as described by Tomi- naga and Ohnishi [22]. Briefly, anaesthetized rats were stabilized in a smooth plane in a prone position. Following a vertical midline skin incision, sagittal and left coronal sutures were identified. Periosteum of left parietal region was peeled away from the midline and tempo- ral muscle was dissected to uncover the temporal bone from its at-