Introduction: Internal jugular vein (IJV) compression has been shown to reduce pathological markers of traumatic brain injury (TBI). However, this novel preventative approach to managing TBI raises concerns of worsening hemorrhage due to the resultant venous congestion. This study aims to test the hypothesis that IJV compression increases hemorrhage after controlled cortical impact (CCI) injury in the swine model.

Methods: 12 swine were randomized to placement of a bilateral IJV compression collar or no collar (control) prior to a right frontal CCI injury. A histological grading of the extent of subarachnoid hemorrhage (SAH) was done in a blinded manner to measure the magnitude of hemorrhage in the collar and control animals. Other various measures of TBI histology were also analyzed including: ?-amyloid precursor protein (?-APP) expression, presence of degenerating neurons, extent of cerebral edema, inflammatory infiltrates, and amount of intra-parenchymal hemorrhage.

Results: Following euthanasia five hours after injury, the collared (c) animals exhibited a significant reduction in total subarachnoid hemorrhage score from the control (uc) animals (uc: 7.13 2.2 versus c: 3.58 2.2, p=0.029) and intra-parenchymal hemorrhage score (uc: 3.0 1.3 versus c: 0.7 11.2, p=0.017). There was no statistically significant difference in scoring for the other markers of TBI (APP, neuronal degeneration, cerebral edema, or inflammatory infiltration).

Conclusions: IJV compression prior to injury was shown to reduce hemorrhage (subarachnoid and intra-parenchymal hemorrhage) in the porcine CCI model when applied prior to injury. The previous work, displaying reduced histological markers of TBI, in concert with this promising animal safety trial proposes the feasibility of IJV compression for TBI mitigation in the clinical environment.

Patient Care: Pre-clinical study providing evidence that IJV compression may be a possible prophylactic measure to traumatic brain injury

Learning Objectives: Understand potential of intracranial prophylactic measures to traumatic brain injury care

References: 1. Attinger EO: Wall properties of veins. IEEE Trans Biomed Eng 16:253-261, 1969 2. Bosnjak R, Kordas M: Circulatory effects of internal jugular vein compression: a computer simulation study. Med Biol Eng Comput 40:423-431, 2002 3. Fries G, Wallenfang T, Hennen J, Velthaus M, Heimann A, Schild H, et al:. Occlusion of the pig superior sagittal sinus, bridging and cortical veins: multistep evolution of sinus-vein thrombosis. J Neurosurg 77:127-133, 1992 4. Frydrychowski AF, Winklewski PJ, Guminski W: Influence of acute jugular vein compression on the cerebral blood flow velocity, pial artery pulsation and width of subarachnoid space in humans. PLoS One 7:e48245, 2012 5. Gisolf J, van Lieshout JJ, van Heusden K, Pott F, Stok WJ, Karemaker JM. Human cerebral venous outflow pathway depends on posture and central venous pressure. J Physiol 560:317-327, 2004 6. Grady MS, Bedford RF, Park TS: Changes in superior sagittal sinus pressure in children with head elevation, jugular venous compression, and PEEP. J Neurosurg 65:199-202, 1986 7. Greiner R, Guggenberger W: Buckling behaviour of axially loaded steel cylinders on local supports—with and without internal pressure. Thin-Walled Structures 31:159- 167, 1998. 8. Hoshizaki TB, Post A, Oeur RA, Brien SE: Current and future concepts in helmet and sports injury prevention. Neurosurgery 75 Suppl 4:S136-48, 2014 17 9. Jin G, DeMoya MA, Duggan M, Knightly T, Mejaddam AY, Hwabejire J, et al: Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults. Shock 38:49-56, 2012 10. Jin G, Duggan M, Imam A, Demoya MA, Sillesen M, Hwabejire J, et al: Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury. J Trauma Acute Care Surg 73:1461-1470, 2012 11. Kawajiri H, Furuse M, Namba R, Kotani J, Oka T: Effect of internal jugular vein ligation on resorption of cerebrospinal fluid. J Maxillofac Surg 11:42-45, 1983 12. Kilbaugh TJ, Bhandare S, Lorom DH, Saraswati M, Robertson CL, Margulies SS: Cyclosporin A preserves mitochondrial function after traumatic brain injury in the immature rat and piglet. J Neurotrauma 28:763-74, 2011 13. Langlois JA, Rutland-Brown W, Wald MM: The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21:375-378, 2006 14. Lee AY, Han HC: A Nonlinear Thin-Wall Model for Vein Buckling. Cardiovasc Eng 1:282-289, 2010 15. Lynall RC, Kerr ZY, Parr MS, Hackney AC, Mihalik JP: Division I College Football Concussion Rates Are Higher at Higher Altitudes. J Orthop Sports Phys Ther 46:96-103, 2016 16. Manley GT, Rosenthal G, Lam M, Morabito D, Yan D, Derugin N, et al: Controlled cortical impact in swine: pathophysiology and biomechanics. J Neurotrauma 23:128-139, 2006 17. Martinez R, Fierro CA, Shireman PK, Han HC: Mechanical buckling of veins under internal pressure. Ann Biomed Eng 38:1345-1353, 2010 18 18. Mead R: The Design of Experiments: Statistical Principles for Practical Applications. Cambridge, UK: Cambridge University Press, 1990, p620 19. Miyamoto K, Heimann A, Kempski O: Microcirculatory alterations in a Mongolian gerbil sinus-vein thrombosis model. J Clin Neurosci 8 Suppl 1:97-105, 2001 20. Myer GD, Smith D, Barber Foss KD, Dicesare CA, Kiefer AW, et al: Rates of concussion are lower in National Football League games played at higher altitudes. J Orthop Sports Phys Ther 44:164-172, 2014 21. Mytar J, Kibler KK, Easley RB, Smielewski P, Czosnyka M, Andropoulos DB, et al: Static autoregulation is intact early after severe unilateral brain injury in a neonatal Swine model. Neurosurgery 71:138-145, 2012 22. Nathoo N, Caris EC, Wiener JA, Mendel E: History of the vertebral venous plexus and the significant contributions of Breschet and Batson. Neurosurgery 69:1007- 1014, 2011 23. National Center for Catastrophic Sport Injury Research. Annual Survey of Football Injury Research. National Center for Catastrophic Sport Injury Research, 2014 (https://nccsir.unc.edu/files/2013/10/Annual-Football-2014-Fatalities-Final.pdf) [Accessed February 8, 2016] 24. Nusbaum DM, Clark JB, Brady KM, Kibler KK, Sutton JP, Easley RB: Intracranial pressure and optic nerve sheath diameter as cephalic venous pressure increases in swine. Aviat Space Environ Med 84:946-51, 2013 25. Pudenz RH, Shelden CH: The lucite calvarium; a method for direct observation of the brain; cranial trauma and brain movement. J Neurosurg 3:487-505, 1946 19 26. Rekate HL. Brain turgor (Kb): intrinsic property of the brain to resist distortion. Pediatr Neurosurg 18:257-262, 1992 27. Shah QH, Mujahid M, Al-Atabi M, Abakr Y: Load carrying capablility of liquid filled cylindrical shell structures under axial compression. J Engin Sci Tech 6:516- 529, 2011 28. Smith DW, Bailes JE, Fisher JA, Robles J, Turner RC, Mills JD: Internal jugular vein compression mitigates traumatic axonal injury in a rat model by reducing the intracranial slosh effect. Neurosurgery 70:740-746, 2012 29. Smith DW, Myer GD, Comstock RD, Clark JF, Bailes JE: Altitude Does Not Reduce Concussion Incidence: Response. Orthop J Sports Med 2:2325967114527235, 2014 30. Turner RC, Naser ZJ, Bailes JE, Smith DW, Fisher JA, Rosen CL. Effect of slosh mitigation on histologic markers of traumatic brain injury: laboratory investigation. J Neurosurg 117:1110-1118, 2012 31. Wagner EM, Traystman RJ: Cerebral venous outflow and arterial microsphere flow with elevated venous pressure. Am J Physiol 244:H505-12, 1983 32. Wei EP, Kontos HA: Increased venous pressure causes myogenic constriction of cerebral arterioles during local hyperoxia. Circ Res 55:249-252,1984