VENTRICULAR SYSTEM & BLOOD BRAIN BARRIER

ventricular system of brain
blood brain barier
csf

1. VENTRICULAR SYSTEM, CSF & BLOOD BRAIN BARRIER Dr Hari Ram Sedai 1 st Year Resident Psychiatry

2. OBJECTIVES TO LEARN THE: Location, boundaries, content and function of brain ventricles Location, origins & functions of CSF Structure and function of blood brain barrier & its clinical importance

3. VENTRICULAR SYSTEM The ventricles are four fluid-filled cavities located within the brain Consists of: 2 Lateral ventricles T he Third ventricle The Fourth ventricle

4. LATERAL VENTRICLE Two irregular cavity lying within each cerebral hemisphere C shaped & Consists of: Central / Body - Parietal lobe Anterior horn- Frontal lobe Posterior horn- Occipital lobe Inferior horn- Temporal lobe

5. Body (Central) Part Extends from inter-ventricular foramen posteriorly as far as the posterior end of thalamus Body of lateral ventricles has : Roof Floor Medial wall

6. Roof of Body of Lateral Ventricle Formed by under surface of corpus callosum Floor of body of Lateral Ventricle - Formed by: 1. Caudate nucleus 2. Lateral margin of thalamus 3. Choroidal fissure Medial wall of body of lateral wall - Formed by septum pellucidum anteriorly

7. Anterior Horn Roof - Trunk of corpus callosum Floor - Head of the caudate nucleus and the rostrum of corpus callosum Anterior - G enu of corpus callosum Medial - Septum P ellucidum

8. Posterior Horn Location - Occipital lobe Roof/Lateral wall - Tapetum of Corpus callosum Medially - Two Elevations 1. Bulb of posterior horn by f orceps major (fibres of corpus callosum) 2. Calcar avis by calcarine sulcus

9. Inferior Horn - Lies in Temporal lobe Roof (Above & laterally) 1.Tapetum 2.Tail of caudate nucleus 3.Amygdaloid nucleus Floor( Below & Medially) 1.Hippocampus 2.Fimbria of hippocampus, collateral eminence

10. THIRD VENTRICLE Slit like cleft between the two thalami & a part of hypothalamus Roof - Fornix, tella chorodia Floor - optic chiasma , infundibulum (pituitary stalk) mammillary bodies, tegmentum of mid brain Laterally - Thalamus, Hypothalamus Anteriorly - Lamina terminalis , Anterior commissure Posteriorly - Opening in cerebral aqueduct, posterior commissure, pineal recesses, habenular commissure

11. THIRD VENTRICLE

12. FOURTH VENTRICLE Tent shaped cavity filled with CSF Situated dorsal to the pons and upper part of medulla oblongata and ventral to the cerebellum Fourth ventricle is bounded by Two lateral walls Roof or dorsal wall Floor or ventral wall

13. A) Lateral Wall Upper part of lateral wall is formed by the superior cerebellar  peduncle. Lower  part of lateral wall is formed by the inferior cerebellar peduncle B) Floor or Ventral W all ( Rhomboid Fossa) Formed by Dorsal surface of pons and upper open part of the medulla D ivided into two symmetrical halves by the median sulcus Each half is further subdivided by sulcus limitans  into a medial area called medial eminence and lateral vestibular area

14. C) Roof Diamond shaped & d ivided into upper and lower part Upper part- formed by superior medullary velum Lower part- formed by ependyma covered by double layer of pia matter which forms the tela choroidea of fourth ventricle

15. FORAMENS CONNECTING THE VENTRICLES Inter-ventricular foramina (of Monro ) : in each lateral ventricle connect them with 3 rd ventricle Cerebral aqueduct (of Sylvius ) : Connects 3 rd ventricle with 4 th ventricle Foramen of Magendie : Connects 4 th ventricle with central canal of spinal cord Foramina of Luschka on each side of 4 th ventricle connects it to the subarachnoid space around brain & spinal cord

16. PSYCHIATRIC IMPLICATION 1 . Schizophrenia Abnormalities in the ventricular system, particularly enlarged ventricles, have been observed in patients with schizophrenia. Ventricular Enlargement: Often correlates with negative symptoms (e.g., flat affect, social withdrawal) and cognitive deficits. Pathophysiology: Enlargement may indicate loss of brain tissue or disruption in CSF flow dynamics, contributing to the onset or progression of schizophrenia. 2 . Mood Disorders Alterations in the ventricular system have been noted in mood disorders, including bipolar disorder and major depressive disorder (MDD). Bipolar Disorder: Enlargement of the lateral ventricles has been reported, potentially linked to mood dysregulation and cognitive impairment. Major Depressive Disorder: Ventricular enlargement is less consistently reported but may be associated with severe or chronic cases.

17. 3. Neurodevelopmental Disorders Ventricular system abnormalities are also implicated in various neurodevelopmental disorders. Autism Spectrum Disorder (ASD): Some studies suggest increased ventricle size in individuals with ASD, which may be related to developmental disruptions in brain connectivity. Attention-Deficit/Hyperactivity Disorder (ADHD): Ventricular enlargement has been less frequently associated but may occur in some cases, reflecting broader neurodevelopmental anomalies.

18. 4 . Traumatic Brain Injury (TBI) TBIs can lead to secondary ventricular system dysfunction, such as post-traumatic hydrocephalus. Symptoms: Cognitive impairment, personality changes, and emotional dysregulation . Psychiatric Disorders: Increased risk of developing depression, anxiety, and post-traumatic stress disorder (PTSD ) 5 . Neurodegenerative Disorders Conditions like Alzheimer's disease and other dementias often involve ventricular enlargement due to brain atrophy. Alzheimer's Disease: progressive enlargement of the ventricles, particularly the lateral ventricles. This is typically associated with generalized brain atrophy, including significant loss of grey and white matter Dementia: Similar patterns of ventricular enlargement can be observed, reflecting underlying neurodegenerative processes.

19. CEREBROSPINAL FLUID (CSF) F ound in the ventricles of the brain & subarachnoid space around the brain and spinal cord It has a volume of about 150 ml Rate of CSF production 550ml/day Recycled around 3.7 times/day Normal pressure 70-180 mm H2O

20. FORMATION Most of the CSF is formed by C horoid P lexus of lateral ventricles Lesser formed in third and fourth ventricles Also formed by capillaries on surface of brain and spinal cord

21. Chor0iod P lexus

22. CHOROID PLEXUS C onsists of modified e pendymal cells surrounding a core of capillaries and loose connective tissue These cells are responsible for secreting most of the cerebrospinal fluid in the central nervous system . The epithelial layer of the choroid plexus is continuous with the ependymal cell layer that lines the ventricular system. The epithelial cells have tight junctions on the side facing the ventricle, which acts as a blood-CSF barrier, preventing most substances from crossing into the CSF

23. CSF is formed continuously by the choroid plexus in two stages: First -Plasma is passively filtered across the choroidal capillary endothelium. Next - Secretion of water and ions across the choroidal epithelium provides for active control of CSF composition and quantity Bicarbonate , chloride, and potassium ions enter the CSF via channels in the epithelial cell apical membranes. Aquaporins provide for water movement to balance osmotic gradients

24. FORMATION OF CSF Net transport of Na+ & Cl - across the epithelium results in secretion of CSF Cl - efflux from the epithelium is mediated by a co-transporter Generation of H+ & HCO3 by carbonic anhydrase is important in secretion of CSF

25. CIRCULATION

26. ABSORPTION Occurs in arachnoid v illi that project into the d ural venous sinuses, especially the superior sagittal sinus CSF absorption into the venous sinuses occurs when CSF pressure exceeds the venous pressure in the sinus Some CSF is absorbed directly into the veins in the subarachnoid space

27. FUNCTIONS OF CSF 1. Cushions and protects the central nervous system from trauma 2. Provides mechanical buoyancy and support for the brain 3. Serves as a reservoir and assists in the regulation of the contents of the skull 4. Nourishes the central nervous system S. Removes metabolites from the central nervous system 6. Serves as a pathway for pineal secretions to reach the pituitary gland

28. CSF Diagnostics : Schizophrenia and Psychiatric disorders Orlovska-Waast , S., Köhler -Forsberg, O., Brix, S.W.   et al . a systematic review and meta-analysis.   Mol Psychiatry    24 , 869–887 (2019) Studies have shown that a mild neuroinflammatory response can be observed in the CSF in certain psychiatric disorders, such as schizophrenia and bipolar disorder . These findings suggest that an immune-mediated component may be involved in the pathophysiology of these disorders. Fundamentals of CSF diagnosis in psychiatric disorders include protein analysis (albumin, IgG , IgA, IgM ) and oligoclonal IgG and lactate analysis. Parallel analysis of CSF with serum samples form the basis for interpretation of immunoglobulin patterns in Reiber diagrams and compilation of data in the cumulative CSF data report for the individual patient. Recent CSF studies in severe mental illness indicate that approximately 79% of treatment-resistant cases with affective or schizophrenic spectrum disorders showed minor CSF abnormalities . The meta-analysis by Orlovska-Waast et al. (2019) published in Nature summarized various neuroinflammatory markers in schizophrenia and affective disorders. Thus, CSF total protein was elevated in both schizophrenia and affective disorders, CSF/serum ratio of IgG was elevated in schizophrenia, while IgG /albumin ratio was decreased

29. BLOOD-BRAIN BARRIER Continuous lipid bilayer that encircles the endothelial cells and isolates the brain tissue from the blood 1) Endothelial cells in the wall of the capillary 2 ) C ontinuous basement membrane surrounding the capillary outside the endothelial cells 3 ) F oot processes of the astrocytes that adhere to the outer surface of the capillary wall

30. BLOOD-BRAIN BARRIER Membrane that controls passage of substances from blood into the central nervous system

31. BLOOD-BRAIN BARIER A) Endothelial layer: Presence of tight junctions Impermeable to most substances Increased expression of transport & carrier proteins: receptor mediated endocytosis Absence of fenestrations

32. Tight junctions: Claudins - Back bone of tight junction, forms dimers & bind homotypically on adjacent cells to produce primary seal of the tight junction Occludin - Function as primary regulatory protein Junctional adhesion molecule- Regulate leukocyte migration across BBB Pericytes : - L ies adjacent to capillaries - Helps in regulation of endothelial proliferation, angiogenesis & inflammatory process

33. Clinical Implications of the Blood-Brain Barrier Clinicians must know the degree to which drugs penetrate the brain in order to treat diseases of the nervous system intelligently. I t is clinically relevant that the amines dopamine and serotonin penetrate brain tissue to a very limited degree but their corresponding acid precursors, L-dopa and 5-hydroxytryptophan enter with relative ease

34. CIRCUMVENTRICULAR ORGANS

35. UNDERSTANDING THE ROLE OF THE LEAKY BLOOD-BRAIN BARRIER IN EPILEPSY BBB leakage, which is associated with an increase in the chemical messenger glutamate, has been suggested in the process of developing epilepsy Leaky BBB is thought to affect anti seizure drug resistance due to the influx of serum proteins that can bind to drugs and reduce their effectiveness in the brain Rempe RG, et al.,  Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.  J Neurosci . 2018 May2;38(18):4301-4315.

36. REFERENCES Snells’s clinical neuroanatomy 8 th edition Ganong's Review of Medical Physiology, 23rd Edition BD Chaurasia’s human anatomy 8 th edition Orlovska-Waast , S., Köhler -Forsberg, O., Brix, S.W.   et al.   Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis.   Mol Psychiatry    24 , 869–887 (2019).   https://doi.org/10.1038/s41380-018-0220-4 Rempe RG, et al.,  Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.  J Neurosci . 2018 May2;38(18):4301-4315 . Andreasen , N. C., et al. (1982). "Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms." American Journal of Psychiatry , 139(3), 297-302 Strakowski , S. M., et al. (2002). "Brain magnetic resonance imaging of structural abnormalities in bipolar disorder." Archives of General Psychiatry , 59(6), 505-512 Jack, C. R., et al. (1992). "MR-based hippocampal volumetry in the diagnosis of Alzheimer's disease." Neurology , 42(1), 183-188