Pathology Snapshot: Architecture and Function of the Human Brain

As the core of the central nervous system, brain parenchyma serves as the “supreme command center” for human regulation and control. Its exquisite cytoarchitecture and specialized tissue functions underlie complex physiological processes such as perception, movement, and cognition. By integrating neuro-anatomical hallmarks, this review systematically outlines the key structural-functional units and their associated pathological alterations, providing a foundation for understanding neurological disorders.

 

I. Neuro-anatomical Core Structures & Functions

Enclosed within the cranial cavity, brain parenchyma is subdivided into four macro-regions—telencephalon, diencephalon, brainstem and cerebellum—which operate both autonomously and cooperatively to form an integrated neural governance network.

 

(A) Telencephalon: Supratentorial Higher-Order Processing Center

The telencephalon, the largest compartment, consists of two cerebral hemispheres interconnected by the corpus callosum and constitutes the principal substrate for higher cognition.

 

1. Superficial Cytoarchitecture & Functional Parcellation

• Cerebral cortex: a laminar grey-mantle rich in neuronal somata; convoluted sulco-gyral pattern expands surface area. Lobular parcellation:
• Frontal lobe: voluntary motor control, executive cognition (decision-making, planning), language production (Broca’s area);
• Parietal lobe: somatosensation, spatial orientation, attention;
• Temporal lobe: auditory processing, memory consolidation, language comprehension (Wernicke’s area);
• Occipital lobe: primary visual integration;
• Insula: viscerosensation & emotional modulation.

2. Deep Structures

• Cerebral medulla: subcortical white matter composed of projection, commissural (corpus callosum) and association fibres;
• Basal ganglia: deep-grey nuclei (striatum, globus pallidus, subthalamic nucleus, substantia nigra) modulating motor rhythm, emotion and cognition;
• Lateral ventricles: CSF-filled cavities participating in metabolic waste clearance and intracranial pressure homeostasis.

 

(B) Diencephalon: Neuro-endocrine Relay Hub

Positioned between midbrain and telencephalon, the diencephalon is largely covered by hemispheres and acts as a critical cortico-subcortical gateway.

 

Key Components & Functions:

• Dorsal thalamus: principal sensory relay (except olfaction); all ascending sensory tracts synapse here before cortical projection;
• Hypothalamus: neuro-endocrine integrator regulating thermoregulation, feeding, water balance, endocrine output and affective behaviour; linked to pituitary via infundibulum;
• Metathalamus: medial & lateral geniculate bodies—auditory and visual relays, respectively;
• Epithalamus: modulates circadian rhythms;
• Subthalamus: collaborates with basal ganglia in motor modulation.

 

(C) Brainstem: Vital Centre & Conduction Tract

Extending from diencephalon to spinal cord, the brainstem (midbrain, pons, medulla) occupies the posterior cranial fossa and serves as the principal conduit between spinal cord, cerebellum and cerebrum.

Core Functions

• Vital centres: medullary cardiovascular & respiratory nuclei regulate basic life-sustaining activities;
• Conduction: all ascending sensory and descending motor tracts traverse the brainstem;
• Cranial nerve nuclei: house nuclei of CN III–XII, governing head & neck sensorimotor functions;
• Reticular formation: centrally located neuronal mesh maintaining arousal, sleep–wake cycles and attention.

(D) Cerebellum: Motor Coordination & Equilibrium Centre

Located dorsal to pons & medulla, the cerebellum comprises a surface cortical grey mantle and internal white matter embedding deep cerebellar nuclei.

• Core functions: maintenance of balance, modulation of muscle tone, coordination of voluntary movement (fine motor skills, gait). Connected to brainstem via superior, middle and inferior cerebellar peduncles for feed-back motor control.

 

II. Brain Parenchyma Sectioning Planes

The most commonly used neuro-anatomical planes are coronal, sagittal and horizontal.

 

III. Common Neuropathological Alterations & Associated Disorders

Neuropathological changes typically involve neuronal loss, axonal injury, inflammatory infiltration or structural malformations. Lesion topography dictates clinical phenotype. Core entities are summarised below:

(A) Telencephalic Disorders

Disease Entity	Key Neuropathology	Core Clinical Phenotype	Lesion Localisation / Mechanism
Alzheimer’s disease	Massive neuronal loss in cortex & hippocampus; senile plaques (β-amyloid) and neurofibrillary tangles (hyper-phosphorylated tau).	Progressive memory loss, cognitive decline, personality change.	Frontal, temporal, hippocampal regions; cholinergic deficit.
Ischaemic stroke (cerebral infarction)	Ischaemic necrosis in internal capsule & MCA territory; neuronal lysis, gliosis.	Contralateral hemiplegia, hemisensory loss, homonymous hemianopia.	Projection-fibre dense areas (e.g. internal capsule); vascular occlusion.
Epilepsy	Abnormal synchronous cortical discharges; hippocampal sclerosis or cortical dysplasia in subsets.	Recurrent seizures (convulsions, impaired consciousness).	Frontal & temporal cortices; neuronal hyper-excitability.
Parkinson’s disease	Loss of nigral dopaminergic neurons; Lewy bodies (α-synuclein).	Resting tremor, rigidity, bradykinesia.	Striato-nigral pathway; dopamine depletion.

 

(B) Diencephalic Disorders

Disease Entity	Key Neuropathology	Core Clinical Phenotype	Lesion Localisation / Mechanism
Hypothalamic hamartoma	Developmental malformation forming a benign tumour-like nodule.	Precocious puberty, gelastic seizures, behavioural anomalies.	Tuber cinereum; hormonal dysregulation.
Thalamic infarction	Ischaemic necrosis of dorsal thalamus.	Contralateral sensory deficit (pain, temperature, proprioception).	Ventral posterior nucleus; thalamogeniculate artery occlusion.
Diabetes insipidus	Degeneration of supraoptic & paraventricular neurons → ADH deficiency.	Polydipsia, polyuria, dilute urine.	Hypothalamo-neurohypophyseal tract lesion.

 

(C) Brainstem Disorders

Disease Entity	Key Neuropathology	Core Clinical Phenotype	Lesion Localisation / Mechanism
Brainstem infarction	Focal ischaemic necrosis involving cranial-nerve nuclei or tracts.	Crossed hemiplegia (ipsilateral face + contralateral limb), dysphagia.	Respective brainstem segment; basilar artery branch occlusion.
Brainstem glioma	Malignant proliferation of intrinsic glial cells.	Progressive limb weakness, cranial neuropathies, respiratory compromise.	Pons most frequent; compression/invasion of nuclei & tracts.
Multiple sclerosis	Auto-immune demyelination of CNS white matter; brainstem commonly affected.	Relapsing limb weakness, internuclear ophthalmoplegia, sensory disturbances.	Brainstem white-matter plaques; immune-mediated myelin attack.

 

(D) Cerebellar Disorders

Disease Entity	Key Neuropathology	Core Clinical Phenotype	Lesion Localisation / Mechanism
Cerebellar infarction / haemorrhage	Vascular occlusion or rupture within cerebellar hemisphere or vermis.	Vertigo, ataxia, nystagmus.	Territories of PICA or SCA.
Spinocerebellar ataxia	Genetic neurodegeneration of cerebellum & spinocerebellar tracts.	Progressive ataxia, gait disturbance, dysarthria.	Cerebellar cortex & medulla; gene-driven axonopathy.
Cerebellar tumours (e.g. medulloblastoma)	Malignant embryonal tumour, predominantly in children.	Headache, vomiting (↑ICP), truncal ataxia.	Vermis; compression of 4th ventricle → obstructive hydrocephalus.

 

Core mIHC Panel for Brain Tissue

Target	Category	Diagnostic Value	Related Disorders
NeuN	Neuronal marker	Labels mature neuronal nuclei; quantifies neuronal loss / survival.	Alzheimer’s disease, cerebral infarction
GFAP	Glial marker	Labels astrocytes; indicates gliosis / glial scar.	Traumatic brain injury, multiple sclerosis
Iba1	Immune marker	Labels microglia; assesses neuro-inflammation.	Encephalitis, brain tumours
β-amyloid	Pathology protein	Detects senile plaques in Alzheimer’s disease.	Alzheimer’s disease
Tau (p-Tau)	Pathology protein	Detects neurofibrillary tangles.	Alzheimer’s disease, frontotemporal dementia
α-synuclein	Pathology protein	Detects Lewy bodies in Parkinson’s disease.	Parkinson’s disease, dementia with Lewy bodies
MBP	Myelin marker	Evaluates extent of demyelination.	Multiple sclerosis, leukodystrophies
CD3	Immune marker	Labels T-lymphocyte infiltration.	Autoimmune encephalitis, CNS lymphoma
Nestin	Neural stem-cell marker	Assesses endogenous repair potential after injury.	Post-stroke reparative phase, TBI
PD-L1	Immune-checkpoint marker	Screens eligibility for immune-checkpoint inhibitors.	Glioblastoma

 

Mouse hippocampal mIHC (NeuN pink + GFAP green + Iba1 red)